---
_id: '10321'
abstract:
- lang: eng
text: Mosaic analysis with double markers (MADM) technology enables the generation
of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling
and introduction of a mutation of a gene of interest with single-cell resolution.
This protocol highlights major steps for the generation of genetic mosaic tissue
and the isolation and processing of respective tissues for downstream histological
analysis. For complete details on the use and execution of this protocol, please
refer to Contreras et al. (2021).
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: This research was supported by the Scientific Service Units (SSU)
at IST Austria through resources provided by the Bioimaging (BIF) and Preclinical
Facilities (PCF). We particularly thank Mohammad Goudarzi for assistance with photography
of mouse perfusion and dissection. N.A. received support from FWF Firnberg-Programm
(T 1031). This work was also supported by IST Austria institutional funds; FWF SFB
F78 to S.H.; and the European Research Council (ERC) under the European Union’s
Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro)
to S.H.
article_number: '100939'
article_processing_charge: Yes
article_type: original
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Hippenmeyer S. Genetic mosaic dissection of candidate genes in mice
using mosaic analysis with double markers. STAR Protocols. 2021;2(4). doi:10.1016/j.xpro.2021.100939
apa: Amberg, N., & Hippenmeyer, S. (2021). Genetic mosaic dissection of candidate
genes in mice using mosaic analysis with double markers. STAR Protocols.
Cell Press. https://doi.org/10.1016/j.xpro.2021.100939
chicago: Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate
Genes in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols.
Cell Press, 2021. https://doi.org/10.1016/j.xpro.2021.100939.
ieee: N. Amberg and S. Hippenmeyer, “Genetic mosaic dissection of candidate genes
in mice using mosaic analysis with double markers,” STAR Protocols, vol.
2, no. 4. Cell Press, 2021.
ista: Amberg N, Hippenmeyer S. 2021. Genetic mosaic dissection of candidate genes
in mice using mosaic analysis with double markers. STAR Protocols. 2(4), 100939.
mla: Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate
Genes in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols,
vol. 2, no. 4, 100939, Cell Press, 2021, doi:10.1016/j.xpro.2021.100939.
short: N. Amberg, S. Hippenmeyer, STAR Protocols 2 (2021).
date_created: 2021-11-21T23:01:28Z
date_published: 2021-11-10T00:00:00Z
date_updated: 2023-11-16T13:08:03Z
day: '10'
ddc:
- '573'
department:
- _id: SiHi
doi: 10.1016/j.xpro.2021.100939
ec_funded: 1
file:
- access_level: open_access
checksum: 9e3f6d06bf583e7a8b6a9e9a60500a28
content_type: application/pdf
creator: cchlebak
date_created: 2021-11-22T08:23:58Z
date_updated: 2021-11-22T08:23:58Z
file_id: '10329'
file_name: 2021_STARProtocols_Amberg.pdf
file_size: 7309464
relation: main_file
success: 1
file_date_updated: 2021-11-22T08:23:58Z
has_accepted_license: '1'
intvolume: ' 2'
issue: '4'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
publication: STAR Protocols
publication_identifier:
eissn:
- 2666-1667
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Genetic mosaic dissection of candidate genes in mice using mosaic analysis
with double markers
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 2
year: '2021'
...
---
_id: '10655'
abstract:
- lang: eng
text: "Adeno-associated viruses (AAVs) are widely used to deliver genetic material
in vivo to distinct cell types such as neurons or glial cells, allowing for targeted
manipulation. Transduction of microglia is mostly excluded from this strategy,
likely due to the cells’ heterogeneous state upon environmental changes, which
makes AAV design challenging. Here, we established the retina as a model system
for microglial AAV validation and optimization. First, we show that AAV2/6 transduced
microglia in both synaptic layers, where layer preference corresponds to the intravitreal
or subretinal delivery method. Surprisingly, we observed significantly enhanced
microglial transduction during photoreceptor degeneration. Thus, we modified the
AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E,
R576Q, K493S, and K459S), resulting in increased microglial transduction in the
outer plexiform layer. Finally, to improve microglial-specific transduction, we
validated a Cre-dependent transgene delivery cassette for use in combination with
the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future
studies optimizing AAV-mediated microglia transduction and highlight that environmental
conditions influence microglial transduction efficiency.\r\n"
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement no. 715571). The research was supported by the Scientific Service
Units (SSU) of IST Austria through resources provided by the Bioimaging Facility,
the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger
and Michael Schunn for their animal colony management and support. We would also
like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally,
we would like to thank the Siegert team members for discussion about the manuscript.
article_processing_charge: Yes
article_type: original
author:
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Gabriele M.
full_name: Wögenstein, Gabriele M.
last_name: Wögenstein
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Raquel
full_name: Casado Polanco, Raquel
id: 15240fc1-dbcd-11ea-9d1d-ac5a786425fd
last_name: Casado Polanco
orcid: 0000-0001-8293-4568
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
2021;23:210-224. doi:10.1016/j.omtm.2021.09.006
apa: Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., & Siegert,
S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency
in the photoreceptor degenerative environment. Molecular Therapy - Methods
and Clinical Development. Elsevier. https://doi.org/10.1016/j.omtm.2021.09.006
chicago: Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado
Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development. Elsevier, 2021. https://doi.org/10.1016/j.omtm.2021.09.006.
ieee: M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert,
“Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment,” Molecular Therapy - Methods and Clinical
Development, vol. 23. Elsevier, pp. 210–224, 2021.
ista: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
23, 210–224.
mla: Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development, vol. 23, Elsevier, 2021, pp. 210–24,
doi:10.1016/j.omtm.2021.09.006.
short: M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular
Therapy - Methods and Clinical Development 23 (2021) 210–224.
date_created: 2022-01-23T23:01:28Z
date_published: 2021-12-10T00:00:00Z
date_updated: 2023-11-16T13:12:03Z
day: '10'
ddc:
- '570'
department:
- _id: SaSi
- _id: SiHi
doi: 10.1016/j.omtm.2021.09.006
ec_funded: 1
external_id:
isi:
- '000748748500019'
file:
- access_level: open_access
checksum: 77dc540e8011c5475031bdf6ccef20a6
content_type: application/pdf
creator: cchlebak
date_created: 2022-01-24T07:43:09Z
date_updated: 2022-01-24T07:43:09Z
file_id: '10657'
file_name: 2021_MolTherMethodsClinDev_Maes.pdf
file_size: 4794147
relation: main_file
success: 1
file_date_updated: 2022-01-24T07:43:09Z
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 210-224
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Molecular Therapy - Methods and Clinical Development
publication_identifier:
eissn:
- 2329-0501
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2021'
...
---
_id: '7800'
abstract:
- lang: eng
text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
(CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models
to evaluate the consequences of Cul3 mutations in vivo. Our results show that
Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as
ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical
lamination abnormalities due to defective neuronal migration and reduced numbers
of excitatory and inhibitory neurons. In line with the observed abnormal columnar
organization, Cul3 haploinsufficiency is associated with decreased spontaneous
excitatory and inhibitory activity in the cortex. At the molecular level, employing
a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and
adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal
proteins in Cul3 mutant neuronal cells results in atypical organization of the
actin mesh at the cell leading edge, likely causing the observed migration deficits.
In contrast to these important functions early in development, Cul3 deficiency
appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency
in adult mice does not result in the behavioral defects observed in constitutive
Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has
a critical role in the regulation of cytoskeletal proteins and neuronal migration
and that ASD-associated defects and behavioral abnormalities are primarily due
to Cul3 functions at early developmental stages.
acknowledged_ssus:
- _id: PreCl
article_processing_charge: No
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Zoe
full_name: Dobler, Zoe
id: D23090A2-9057-11EA-883A-A8396FC7A38F
last_name: Dobler
- first_name: Emanuele
full_name: Cacci, Emanuele
last_name: Cacci
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
homeostasis and cell migration during a critical window of brain development.
bioRxiv. doi:10.1101/2020.01.10.902064
apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer,
C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development. bioRxiv.
Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064
chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates
Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of
Brain Development.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.01.10.902064 .
ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development,” bioRxiv.
Cold Spring Harbor Laboratory.
ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger
C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton
protein homeostasis and cell migration during a critical window of brain development.
bioRxiv, 10.1101/2020.01.10.902064
.
mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
and Cell Migration during a Critical Window of Brain Development.” BioRxiv,
Cold Spring Harbor Laboratory, doi:10.1101/2020.01.10.902064 .
short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer,
C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv
(n.d.).
date_created: 2020-05-05T14:31:33Z
date_published: 2020-01-11T00:00:00Z
date_updated: 2024-09-10T12:04:26Z
day: '11'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
- _id: LifeSc
doi: '10.1101/2020.01.10.902064 '
file:
- access_level: open_access
checksum: c6799ab5daba80efe8e2ed63c15f8c81
content_type: application/pdf
creator: rsix
date_created: 2020-05-05T14:31:19Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7801'
file_name: 2020.01.10.902064v1.full.pdf
file_size: 2931370
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Preprint
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '8620'
relation: dissertation_contains
status: public
- id: '9429'
relation: later_version
status: public
status: public
title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a
critical window of brain development
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '7814'
abstract:
- lang: eng
text: 'Scientific research is to date largely restricted to wealthy laboratories
in developed nations due to the necessity of complex and expensive equipment.
This inequality limits the capacity of science to be used as a diplomatic channel.
Maker movements use open-source technologies including additive manufacturing
(3D printing) and laser cutting, together with low-cost computers for developing
novel products. This movement is setting the groundwork for a revolution, allowing
scientific equipment to be sourced at a fraction of the cost and has the potential
to increase the availability of equipment for scientists around the world. Science
education is increasingly recognized as another channel for science diplomacy.
In this perspective, we introduce the idea that the Maker movement and open-source
technologies have the potential to revolutionize science, technology, engineering
and mathematics (STEM) education worldwide. We present an open-source STEM didactic
tool called SCOPES (Sparking Curiosity through Open-source Platforms in Education
and Science). SCOPES is self-contained, independent of local resources, and cost-effective.
SCOPES can be adapted to communicate complex subjects from genetics to neurobiology,
perform real-world biological experiments and explore digitized scientific samples.
We envision such platforms will enhance science diplomacy by providing a means
for scientists to share their findings with classrooms and for educators to incorporate
didactic concepts into STEM lessons. By providing students the opportunity to
design, perform, and share scientific experiments, students also experience firsthand
the benefits of a multinational scientific community. We provide instructions
on how to build and use SCOPES on our webpage: http://scopeseducation.org.'
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
- _id: EM-Fac
article_number: '48'
article_processing_charge: No
article_type: original
author:
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
citation:
ama: 'Beattie RJ, Hippenmeyer S, Pauler F. SCOPES: Sparking curiosity through Open-Source
platforms in education and science. Frontiers in Education. 2020;5. doi:10.3389/feduc.2020.00048'
apa: 'Beattie, R. J., Hippenmeyer, S., & Pauler, F. (2020). SCOPES: Sparking
curiosity through Open-Source platforms in education and science. Frontiers
in Education. Frontiers Media. https://doi.org/10.3389/feduc.2020.00048'
chicago: 'Beattie, Robert J, Simon Hippenmeyer, and Florian Pauler. “SCOPES: Sparking
Curiosity through Open-Source Platforms in Education and Science.” Frontiers
in Education. Frontiers Media, 2020. https://doi.org/10.3389/feduc.2020.00048.'
ieee: 'R. J. Beattie, S. Hippenmeyer, and F. Pauler, “SCOPES: Sparking curiosity
through Open-Source platforms in education and science,” Frontiers in Education,
vol. 5. Frontiers Media, 2020.'
ista: 'Beattie RJ, Hippenmeyer S, Pauler F. 2020. SCOPES: Sparking curiosity through
Open-Source platforms in education and science. Frontiers in Education. 5, 48.'
mla: 'Beattie, Robert J., et al. “SCOPES: Sparking Curiosity through Open-Source
Platforms in Education and Science.” Frontiers in Education, vol. 5, 48,
Frontiers Media, 2020, doi:10.3389/feduc.2020.00048.'
short: R.J. Beattie, S. Hippenmeyer, F. Pauler, Frontiers in Education 5 (2020).
date_created: 2020-05-11T08:18:48Z
date_published: 2020-05-08T00:00:00Z
date_updated: 2021-01-12T08:15:42Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3389/feduc.2020.00048
ec_funded: 1
file:
- access_level: open_access
checksum: a24ec24e38d843341ae620ec76c53688
content_type: application/pdf
creator: dernst
date_created: 2020-05-11T11:34:08Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7818'
file_name: 2020_FrontiersEduc_Beattie.pdf
file_size: 1402146
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
intvolume: ' 5'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Frontiers in Education
publication_identifier:
issn:
- 2504-284X
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
status: public
title: 'SCOPES: Sparking curiosity through Open-Source platforms in education and
science'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2020'
...
---
_id: '7815'
abstract:
- lang: eng
text: Beginning from a limited pool of progenitors, the mammalian cerebral cortex
forms highly organized functional neural circuits. However, the underlying cellular
and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs)
and eventual production of neurons and glia in the developing neuroepithelium
remains unclear. Methods to trace NSC division patterns and map the lineage of
clonally related cells have advanced dramatically. However, many contemporary
lineage tracing techniques suffer from the lack of cellular resolution of progeny
cell fate, which is essential for deciphering progenitor cell division patterns.
Presented is a protocol using mosaic analysis with double markers (MADM) to perform
in vivo clonal analysis. MADM concomitantly manipulates individual progenitor
cells and visualizes precise division patterns and lineage progression at unprecedented
single cell resolution. MADM-based interchromosomal recombination events during
the G2-X phase of mitosis, together with temporally inducible CreERT2, provide
exact information on the birth dates of clones and their division patterns. Thus,
MADM lineage tracing provides unprecedented qualitative and quantitative optical
readouts of the proliferation mode of stem cell progenitors at the single cell
level. MADM also allows for examination of the mechanisms and functional requirements
of candidate genes in NSC lineage progression. This method is unique in that comparative
analysis of control and mutant subclones can be performed in the same tissue environment
in vivo. Here, the protocol is described in detail, and experimental paradigms
to employ MADM for clonal analysis and lineage tracing in the developing cerebral
cortex are demonstrated. Importantly, this protocol can be adapted to perform
MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver
is present.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
article_number: e61147
article_processing_charge: No
article_type: original
author:
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis
in developing cerebral cortex using mosaic analysis with double markers (MADM).
Journal of Visual Experiments. 2020;(159). doi:10.3791/61147
apa: Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen,
A. H., & Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing
cerebral cortex using mosaic analysis with double markers (MADM). Journal of
Visual Experiments. MyJove Corporation. https://doi.org/10.3791/61147
chicago: Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena
Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis
in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).”
Journal of Visual Experiments. MyJove Corporation, 2020. https://doi.org/10.3791/61147.
ieee: R. J. Beattie et al., “Lineage tracing and clonal analysis in developing
cerebral cortex using mosaic analysis with double markers (MADM),” Journal
of Visual Experiments, no. 159. MyJove Corporation, 2020.
ista: Beattie RJ, Streicher C, Amberg N, Cheung GT, Contreras X, Hansen AH, Hippenmeyer
S. 2020. Lineage tracing and clonal analysis in developing cerebral cortex using
mosaic analysis with double markers (MADM). Journal of Visual Experiments. (159),
e61147.
mla: Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing
Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal
of Visual Experiments, no. 159, e61147, MyJove Corporation, 2020, doi:10.3791/61147.
short: R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen,
S. Hippenmeyer, Journal of Visual Experiments (2020).
date_created: 2020-05-11T08:31:20Z
date_published: 2020-05-08T00:00:00Z
date_updated: 2024-03-25T23:30:23Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3791/61147
ec_funded: 1
external_id:
isi:
- '000546406600043'
file:
- access_level: open_access
checksum: 3154ea7f90b9fb45e084cd1c2770597d
content_type: application/pdf
creator: rbeattie
date_created: 2020-05-11T08:28:38Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7816'
file_name: jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf
file_size: 1352186
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
isi: 1
issue: '159'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Journal of Visual Experiments
publication_identifier:
issn:
- 1940-087X
publication_status: published
publisher: MyJove Corporation
quality_controlled: '1'
related_material:
record:
- id: '7902'
relation: part_of_dissertation
status: public
scopus_import: '1'
status: public
title: Lineage tracing and clonal analysis in developing cerebral cortex using mosaic
analysis with double markers (MADM)
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '7875'
abstract:
- lang: eng
text: 'Cells navigating through complex tissues face a fundamental challenge: while
multiple protrusions explore different paths, the cell needs to avoid entanglement.
How a cell surveys and then corrects its own shape is poorly understood. Here,
we demonstrate that spatially distinct microtubule dynamics regulate amoeboid
cell migration by locally promoting the retraction of protrusions. In migrating
dendritic cells, local microtubule depolymerization within protrusions remote
from the microtubule organizing center triggers actomyosin contractility controlled
by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin
localization, thereby causing two effects that rate-limit locomotion: (1) impaired
cell edge coordination during path finding and (2) defective adhesion resolution.
Compromised shape control is particularly hindering in geometrically complex microenvironments,
where it leads to entanglement and ultimately fragmentation of the cell body.
We thus demonstrate that microtubules can act as a proprioceptive device: they
sense cell shape and control actomyosin retraction to sustain cellular coherence.'
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: PreCl
acknowledgement: "The authors thank the Scientific Service Units (Life Sciences, Bioimaging,
Preclinical) of the Institute of Science and Technology Austria for excellent support.
This work was funded by the European Research Council (ERC StG 281556 and CoG 724373),
two grants from the Austrian\r\nScience Fund (FWF; P29911 and DK Nanocell W1250-B20
to M. Sixt) and by the German Research Foundation (DFG SFB1032 project B09) to O.
Thorn-Seshold and D. Trauner. J. Renkawitz was supported by ISTFELLOW funding from
the People Program (Marie Curie Actions) of the European Union’s Seventh Framework
Programme (FP7/2007-2013) under the Research Executive Agency grant agreement (291734)
and a European Molecular Biology Organization long-term fellowship (ALTF 1396-2014)
co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409), E. Kiermaier
by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s
Excellence Strategy—EXC 2151—390873048, and H. Hacker by the American Lebanese Syrian
Associated ¨Charities. K.-D. Fischer was supported by the Analysis, Imaging and
Modelling of Neuronal and Inflammatory Processes graduate school funded by the Ministry
of Economics, Science, and Digitisation of the State Saxony-Anhalt and by the European
Funds for Social and Regional Development."
article_number: e201907154
article_processing_charge: No
article_type: original
author:
- first_name: Aglaja
full_name: Kopf, Aglaja
id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
last_name: Kopf
orcid: 0000-0002-2187-6656
- first_name: Jörg
full_name: Renkawitz, Jörg
id: 3F0587C8-F248-11E8-B48F-1D18A9856A87
last_name: Renkawitz
orcid: 0000-0003-2856-3369
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Irute
full_name: Girkontaite, Irute
last_name: Girkontaite
- first_name: Kerry
full_name: Tedford, Kerry
last_name: Tedford
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Oliver
full_name: Thorn-Seshold, Oliver
last_name: Thorn-Seshold
- first_name: Dirk
full_name: Trauner, Dirk
id: E8F27F48-3EBA-11E9-92A1-B709E6697425
last_name: Trauner
- first_name: Hans
full_name: Häcker, Hans
last_name: Häcker
- first_name: Klaus Dieter
full_name: Fischer, Klaus Dieter
last_name: Fischer
- first_name: Eva
full_name: Kiermaier, Eva
id: 3EB04B78-F248-11E8-B48F-1D18A9856A87
last_name: Kiermaier
orcid: 0000-0001-6165-5738
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Kopf A, Renkawitz J, Hauschild R, et al. Microtubules control cellular shape
and coherence in amoeboid migrating cells. The Journal of Cell Biology.
2020;219(6). doi:10.1083/jcb.201907154
apa: Kopf, A., Renkawitz, J., Hauschild, R., Girkontaite, I., Tedford, K., Merrin,
J., … Sixt, M. K. (2020). Microtubules control cellular shape and coherence in
amoeboid migrating cells. The Journal of Cell Biology. Rockefeller University
Press. https://doi.org/10.1083/jcb.201907154
chicago: Kopf, Aglaja, Jörg Renkawitz, Robert Hauschild, Irute Girkontaite, Kerry
Tedford, Jack Merrin, Oliver Thorn-Seshold, et al. “Microtubules Control Cellular
Shape and Coherence in Amoeboid Migrating Cells.” The Journal of Cell Biology.
Rockefeller University Press, 2020. https://doi.org/10.1083/jcb.201907154.
ieee: A. Kopf et al., “Microtubules control cellular shape and coherence
in amoeboid migrating cells,” The Journal of Cell Biology, vol. 219, no.
6. Rockefeller University Press, 2020.
ista: Kopf A, Renkawitz J, Hauschild R, Girkontaite I, Tedford K, Merrin J, Thorn-Seshold
O, Trauner D, Häcker H, Fischer KD, Kiermaier E, Sixt MK. 2020. Microtubules control
cellular shape and coherence in amoeboid migrating cells. The Journal of Cell
Biology. 219(6), e201907154.
mla: Kopf, Aglaja, et al. “Microtubules Control Cellular Shape and Coherence in
Amoeboid Migrating Cells.” The Journal of Cell Biology, vol. 219, no. 6,
e201907154, Rockefeller University Press, 2020, doi:10.1083/jcb.201907154.
short: A. Kopf, J. Renkawitz, R. Hauschild, I. Girkontaite, K. Tedford, J. Merrin,
O. Thorn-Seshold, D. Trauner, H. Häcker, K.D. Fischer, E. Kiermaier, M.K. Sixt,
The Journal of Cell Biology 219 (2020).
date_created: 2020-05-24T22:00:56Z
date_published: 2020-06-01T00:00:00Z
date_updated: 2023-08-21T06:28:17Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
- _id: NanoFab
doi: 10.1083/jcb.201907154
ec_funded: 1
external_id:
isi:
- '000538141100020'
pmid:
- '32379884'
file:
- access_level: open_access
checksum: cb0b9c77842ae1214caade7b77e4d82d
content_type: application/pdf
creator: dernst
date_created: 2020-11-24T13:25:13Z
date_updated: 2020-11-24T13:25:13Z
file_id: '8801'
file_name: 2020_JCellBiol_Kopf.pdf
file_size: 7536712
relation: main_file
success: 1
file_date_updated: 2020-11-24T13:25:13Z
has_accepted_license: '1'
intvolume: ' 219'
isi: 1
issue: '6'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
- _id: 252C3B08-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W 1250-B20
name: Nano-Analytics of Cellular Systems
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 25A48D24-B435-11E9-9278-68D0E5697425
grant_number: ALTF 1396-2014
name: Molecular and system level view of immune cell migration
publication: The Journal of Cell Biology
publication_identifier:
eissn:
- 1540-8140
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microtubules control cellular shape and coherence in amoeboid migrating cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 219
year: '2020'
...
---
_id: '7902'
abstract:
- lang: eng
text: "Mosaic genetic analysis has been widely used in different model organisms
such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific
fashion. More recently, and less easily conducted, mosaic genetic analysis in
mice has also been enabled with the ambition to shed light on human gene function
and disease. These genetic tools are of particular interest, but not restricted
to, the study of the brain. Notably, the MADM technology offers a genetic approach
in mice to visualize and concomitantly manipulate small subsets of genetically
defined cells at a clonal level and single cell resolution. MADM-based analysis
has already advanced the study of genetic mechanisms regulating brain development
and is expected that further MADM-based analysis of genetic alterations will continue
to reveal important insights on the fundamental principles of development and
disease to potentially assist in the development of new therapies or treatments.\r\nIn
summary, this work completed and characterized the necessary genome-wide genetic
tools to perform MADM-based analysis at single cell level of the vast majority
of mouse genes in virtually any cell type and provided a protocol to perform lineage
tracing using the novel MADM resource. Importantly, this work also explored and
revealed novel aspects of biologically relevant events in an in vivo context,
such as the chromosome-specific bias of chromatid sister segregation pattern,
the generation of cell-type diversity in the cerebral cortex and in the cerebellum
and finally, the relevance of the interplay between the cell-autonomous gene function
and cell-non-autonomous (community) effects in radial glial progenitor lineage
progression.\r\nThis work provides a foundation and opens the door to further
elucidating the molecular mechanisms underlying neuronal diversity and astrocyte
generation."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
citation:
ama: Contreras X. Genetic dissection of neural development in health and disease
at single cell resolution. 2020. doi:10.15479/AT:ISTA:7902
apa: Contreras, X. (2020). Genetic dissection of neural development in health
and disease at single cell resolution. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:7902
chicago: Contreras, Ximena. “Genetic Dissection of Neural Development in Health
and Disease at Single Cell Resolution.” Institute of Science and Technology Austria,
2020. https://doi.org/10.15479/AT:ISTA:7902.
ieee: X. Contreras, “Genetic dissection of neural development in health and disease
at single cell resolution,” Institute of Science and Technology Austria, 2020.
ista: Contreras X. 2020. Genetic dissection of neural development in health and
disease at single cell resolution. Institute of Science and Technology Austria.
mla: Contreras, Ximena. Genetic Dissection of Neural Development in Health and
Disease at Single Cell Resolution. Institute of Science and Technology Austria,
2020, doi:10.15479/AT:ISTA:7902.
short: X. Contreras, Genetic Dissection of Neural Development in Health and Disease
at Single Cell Resolution, Institute of Science and Technology Austria, 2020.
date_created: 2020-05-29T08:27:32Z
date_published: 2020-06-05T00:00:00Z
date_updated: 2023-10-18T08:45:16Z
day: '05'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: SiHi
doi: 10.15479/AT:ISTA:7902
ec_funded: 1
file:
- access_level: closed
checksum: 43c172bf006c95b65992d473c7240d13
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: xcontreras
date_created: 2020-06-05T08:18:08Z
date_updated: 2021-06-07T22:30:03Z
embargo_to: open_access
file_id: '7927'
file_name: PhDThesis_Contreras.docx
file_size: 53134142
relation: source_file
- access_level: open_access
checksum: addfed9128271be05cae3608e03a6ec0
content_type: application/pdf
creator: xcontreras
date_created: 2020-06-05T08:18:07Z
date_updated: 2021-06-07T22:30:03Z
embargo: 2021-06-06
file_id: '7928'
file_name: PhDThesis_Contreras.pdf
file_size: 35117191
relation: main_file
file_date_updated: 2021-06-07T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '214'
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '6830'
relation: dissertation_contains
status: public
- id: '28'
relation: dissertation_contains
status: public
- id: '7815'
relation: dissertation_contains
status: public
status: public
supervisor:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
title: Genetic dissection of neural development in health and disease at single cell
resolution
type: dissertation
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8162'
abstract:
- lang: eng
text: In mammalian genomes, a subset of genes is regulated by genomic imprinting,
resulting in silencing of one parental allele. Imprinting is essential for cerebral
cortex development, but prevalence and functional impact in individual cells is
unclear. Here, we determined allelic expression in cortical cell types and established
a quantitative platform to interrogate imprinting in single cells. We created
cells with uniparental chromosome disomy (UPD) containing two copies of either
the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold
overexpressed or not expressed. By genetic labeling of UPD, we determined cellular
phenotypes and transcriptional responses to deregulated imprinted gene expression
at unprecedented single-cell resolution. We discovered an unexpected degree of
cell-type specificity and a novel function of imprinting in the regulation of
cortical astrocyte survival. More generally, our results suggest functional relevance
of imprinted gene expression in glial astrocyte lineage and thus for generating
cortical cell-type diversity.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit), and A. Seitz and P. Moll (Lexogen GmbH) for technical
support; G. Arque, S. Resch, C. Igler, C. Dotter, C. Yahya, Q. Hudson, and D. Andergassen
for initial experiments and/or assistance; D. Barlow, O. Bell, and all members of
the Hippenmeyer lab for discussion; and N. Barton, B. Vicoso, M. Sixt, and L. Luo
for comments on earlier versions of the manuscript. This research was supported
by the Scientific Service Units (SSU) of IST Austria through resources provided
by the Bioimaging Facilities (BIF), Life Science Facilities (LSF), and Preclinical
Facilities (PCF). A.H.H. is a recipient of a DOC fellowship (24812) of the Austrian
Academy of Sciences. N.A. received support from the FWF Firnberg-Programm (T 1031).
R.B. received support from the FWF Meitner-Programm (M 2416). This work was also
supported by IST Austria institutional funds; a NÖ Forschung und Bildung n[f+b]
life science call grant (C13-002) to S.H.; a program grant from the Human Frontiers
Science Program (RGP0053/2014) to S.H.; the People Programme (Marie Curie Actions)
of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant
agreement 618444 to S.H.; and the European Research Council (ERC) under the European
Union’s Horizon 2020 research and innovation program (grant agreement 725780 LinPro)
to S.H.
article_processing_charge: No
article_type: original
author:
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Thomas
full_name: Penz, Thomas
last_name: Penz
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
orcid: 0000-0001-6091-3088
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting
in cerebral cortex. Neuron. 2020;107(6):1160-1179.e9. doi:10.1016/j.neuron.2020.06.031
apa: Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher,
C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral
cortex. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.06.031
chicago: Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi
H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer.
“Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” Neuron.
Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.06.031.
ieee: S. Laukoter et al., “Cell-type specificity of genomic imprinting in
cerebral cortex,” Neuron, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020.
ista: Laukoter S, Pauler F, Beattie RJ, Amberg N, Hansen AH, Streicher C, Penz T,
Bock C, Hippenmeyer S. 2020. Cell-type specificity of genomic imprinting in cerebral
cortex. Neuron. 107(6), 1160–1179.e9.
mla: Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral
Cortex.” Neuron, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:10.1016/j.neuron.2020.06.031.
short: S. Laukoter, F. Pauler, R.J. Beattie, N. Amberg, A.H. Hansen, C. Streicher,
T. Penz, C. Bock, S. Hippenmeyer, Neuron 107 (2020) 1160–1179.e9.
date_created: 2020-07-23T16:03:12Z
date_published: 2020-09-23T00:00:00Z
date_updated: 2023-08-22T08:20:11Z
day: '23'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2020.06.031
ec_funded: 1
external_id:
isi:
- '000579698700006'
file:
- access_level: open_access
checksum: 7becdc16a6317304304631087ae7dd7f
content_type: application/pdf
creator: dernst
date_created: 2020-12-02T09:26:46Z
date_updated: 2020-12-02T09:26:46Z
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file_name: 2020_Neuron_Laukoter.pdf
file_size: 8911830
relation: main_file
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file_date_updated: 2020-12-02T09:26:46Z
has_accepted_license: '1'
intvolume: ' 107'
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issue: '6'
language:
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month: '09'
oa: 1
oa_version: Published Version
page: 1160-1179.e9
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
- _id: 25D7962E-B435-11E9-9278-68D0E5697425
grant_number: RGP0053/2014
name: Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal
Level
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Website
relation: press_release
url: https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/
scopus_import: '1'
status: public
title: Cell-type specificity of genomic imprinting in cerebral cortex
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 107
year: '2020'
...
---
_id: '8261'
abstract:
- lang: eng
text: Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal
CA3 region, but how they process spatial information remains enigmatic. To examine
the role of GCs in spatial coding, we measured excitatory postsynaptic potentials
(EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt.
Intracellular recording from morphologically identified GCs revealed that most
cells were active, but activity level varied over a wide range. Whereas only ∼5%
of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus,
the GC population broadly encodes spatial information, but only a subset relays
this information to the CA3 network. Fourier analysis indicated that GCs received
conjunctive place-grid-like synaptic input, suggesting code conversion in single
neurons. GC firing was correlated with dendritic complexity and intrinsic excitability,
but not extrinsic excitatory input or dendritic cable properties. Thus, functional
maturation may control input-output transformation and spatial code conversion.
acknowledged_ssus:
- _id: M-Shop
- _id: ScienComp
- _id: PreCl
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation program (grant
agreement 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung
(Z 312-B27, Wittgenstein award, P.J.). We thank Gyorgy Buzsáki, Jozsef Csicsvari,
Juan Ramirez Villegas, and Federico Stella for commenting on earlier versions of
this manuscript. We also thank Katie Bittner, Michael Brecht, Albert Lee, Jeffery
Magee, and Alejandro Pernía-Andrade for sharing expertise in in vivo patch-clamp
recording. We are grateful to Florian Marr for cell labeling, cell reconstruction,
and technical assistance; Ben Suter for helpful discussions; Christina Altmutter
for technical support; Eleftheria Kralli-Beller for manuscript editing; and Todor
Asenov (Machine Shop) for device construction. We also thank the Scientific Service
Units (SSUs) of IST Austria (Machine Shop, Scientific Computing, and Preclinical
Facility) for efficient support.
article_processing_charge: No
article_type: original
author:
- first_name: Xiaomin
full_name: Zhang, Xiaomin
id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
last_name: Zhang
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Zhang X, Schlögl A, Jonas PM. Selective routing of spatial information flow
from input to output in hippocampal granule cells. Neuron. 2020;107(6):1212-1225.
doi:10.1016/j.neuron.2020.07.006
apa: Zhang, X., Schlögl, A., & Jonas, P. M. (2020). Selective routing of spatial
information flow from input to output in hippocampal granule cells. Neuron.
Elsevier. https://doi.org/10.1016/j.neuron.2020.07.006
chicago: Zhang, Xiaomin, Alois Schlögl, and Peter M Jonas. “Selective Routing of
Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” Neuron.
Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.07.006.
ieee: X. Zhang, A. Schlögl, and P. M. Jonas, “Selective routing of spatial information
flow from input to output in hippocampal granule cells,” Neuron, vol. 107,
no. 6. Elsevier, pp. 1212–1225, 2020.
ista: Zhang X, Schlögl A, Jonas PM. 2020. Selective routing of spatial information
flow from input to output in hippocampal granule cells. Neuron. 107(6), 1212–1225.
mla: Zhang, Xiaomin, et al. “Selective Routing of Spatial Information Flow from
Input to Output in Hippocampal Granule Cells.” Neuron, vol. 107, no. 6,
Elsevier, 2020, pp. 1212–25, doi:10.1016/j.neuron.2020.07.006.
short: X. Zhang, A. Schlögl, P.M. Jonas, Neuron 107 (2020) 1212–1225.
date_created: 2020-08-14T09:36:05Z
date_published: 2020-09-23T00:00:00Z
date_updated: 2023-08-22T08:30:55Z
day: '23'
ddc:
- '570'
department:
- _id: PeJo
- _id: ScienComp
doi: 10.1016/j.neuron.2020.07.006
ec_funded: 1
external_id:
isi:
- '000579698700009'
pmid:
- '32763145'
file:
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checksum: 44a5960fc083a4cb3488d22224859fdc
content_type: application/pdf
creator: dernst
date_created: 2020-12-04T09:29:21Z
date_updated: 2020-12-04T09:29:21Z
file_id: '8920'
file_name: 2020_Neuron_Zhang.pdf
file_size: 3011120
relation: main_file
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intvolume: ' 107'
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language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 1212-1225
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Website
relation: press_release
url: https://ist.ac.at/en/news/the-bouncer-in-the-brain/
status: public
title: Selective routing of spatial information flow from input to output in hippocampal
granule cells
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 107
year: '2020'
...
---
_id: '8350'
abstract:
- lang: eng
text: "Cytoplasm is a gel-like crowded environment composed of tens of thousands
of macromolecules, organelles, cytoskeletal networks and cytosol. The structure
of the cytoplasm is thought to be highly organized and heterogeneous due to the
crowding of its constituents and their effective compartmentalization. In such
an environment, the diffusive dynamics of the molecules is very restricted, an
effect that is further amplified by clustering and anchoring of molecules. Despite
the jammed nature of the cytoplasm at the microscopic scale, large-scale reorganization
of cytoplasm is essential for important cellular functions, such as nuclear positioning
and cell division. How such mesoscale reorganization of the cytoplasm is achieved,
especially for very large cells such as oocytes or syncytial tissues that can
span hundreds of micrometers in size, has only begun to be understood.\r\nIn this
thesis, I focus on the recent advances in elucidating the molecular, cellular
and biophysical principles underlying cytoplasmic organization across different
scales, structures and species. First, I outline which of these principles have
been identified by reductionist approaches, such as in vitro reconstitution assays,
where boundary conditions and components can be modulated at ease. I then describe
how the theoretical and experimental framework established in these reduced systems
have been applied to their more complex in vivo counterparts, in particular oocytes
and embryonic syncytial structures, and discuss how such complex biological systems
can initiate symmetry breaking and establish patterning.\r\nSpecifically, I examine
an example of large-scale reorganizations taking place in zebrafish embryos, where
extensive cytoplasmic streaming leads to the segregation of cytoplasm from yolk
granules along the animal-vegetal axis of the embryo. Using biophysical experimentation
and theory, I investigate the forces underlying this process, to show that this
process does not rely on cortical actin reorganization, as previously thought,
but instead on a cell-cycle-dependent bulk actin polymerization wave traveling
from the animal to the vegetal pole of the embryo. This wave functions in segregation
by both pulling cytoplasm animally and pushing yolk granules vegetally. Cytoplasm
pulling is mediated by bulk actin network flows exerting friction forces on the
cytoplasm, while yolk granule pushing is achieved by a mechanism closely resembling
actin comet formation on yolk granules. This study defines a novel role of bulk
actin polymerization waves in embryo polarization via cytoplasmic segregation.
Lastly, I describe the cytoplasmic reorganizations taking place during zebrafish
oocyte maturation, where the initial segregation of the cytoplasm and yolk granules
occurs. Here, I demonstrate a previously uncharacterized wave of microtubule aster
formation, traveling the oocyte along the animal-vegetal axis. Further research
is required to determine the role of such microtubule structures in cytoplasmic
reorganizations therein.\r\nCollectively, these studies provide further evidence
for the coupling between cell cytoskeleton and cell cycle machinery, which can
underlie a core self-organizing mechanism for orchestrating large-scale reorganizations
in a cell-cycle-tunable manner, where the modulations of the force-generating
machinery and cytoplasmic mechanics can be harbored to fulfill cellular functions."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: EM-Fac
acknowledgement: "I would have had no fish and hence no results without our wonderful
fish facility crew, Verena Mayer, Eva Schlegl, Andreas Mlak and Matthias Nowak.
Special thanks to Verena for being always happy to help and dealing with our chaotic
schedules in the lab. Danke auch, Verena, für deine Geduld, mit mir auf Deutsch
zu sprechen. Das hat mir sehr geholfen.\r\nSpecial thanks to the Bioimaging and
EM facilities at IST Austria for supporting us every day. Very special thanks would
go to Robert Hauschild for his continuous support on data analysis and also to Jack
Merrin for designing and building microfabricated chambers for the project and for
the various discussions on making zebrafish extracts."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
citation:
ama: Shamipour S. Bulk actin dynamics drive phase segregation in zebrafish oocytes
. 2020. doi:10.15479/AT:ISTA:8350
apa: Shamipour, S. (2020). Bulk actin dynamics drive phase segregation in zebrafish
oocytes . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8350
chicago: Shamipour, Shayan. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish
Oocytes .” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8350.
ieee: S. Shamipour, “Bulk actin dynamics drive phase segregation in zebrafish oocytes
,” Institute of Science and Technology Austria, 2020.
ista: Shamipour S. 2020. Bulk actin dynamics drive phase segregation in zebrafish
oocytes . Institute of Science and Technology Austria.
mla: Shamipour, Shayan. Bulk Actin Dynamics Drive Phase Segregation in Zebrafish
Oocytes . Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8350.
short: S. Shamipour, Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes
, Institute of Science and Technology Austria, 2020.
date_created: 2020-09-09T11:12:10Z
date_published: 2020-09-09T00:00:00Z
date_updated: 2023-09-27T14:16:45Z
day: '09'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: BjHo
- _id: CaHe
doi: 10.15479/AT:ISTA:8350
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date_created: 2020-09-09T11:06:13Z
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language:
- iso: eng
month: '09'
oa: 1
oa_version: None
page: '107'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '661'
relation: part_of_dissertation
status: public
- id: '6508'
relation: part_of_dissertation
status: public
- id: '7001'
relation: part_of_dissertation
status: public
- id: '735'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
title: 'Bulk actin dynamics drive phase segregation in zebrafish oocytes '
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '8620'
abstract:
- lang: eng
text: "The development of the human brain occurs through a tightly regulated series
of dynamic and adaptive processes during prenatal and postnatal life. A disruption
of this strictly orchestrated series of events can lead to a number of neurodevelopmental
conditions, including Autism Spectrum Disorders (ASDs). ASDs are a very common,
etiologically and phenotypically heterogeneous group of disorders sharing the
core symptoms of social interaction and communication deficits and restrictive
and repetitive interests and behaviors. They are estimated to affect one in 59
individuals in the U.S. and, over the last three decades, mutations in more than
a hundred genetic loci have been convincingly linked to ASD pathogenesis. Yet,
for the vast majority of these ASD-risk genes their role during brain development
and precise molecular function still remain elusive.\r\nDe novo loss of function
mutations in the ubiquitin ligase-encoding gene Cullin 3 (CUL3) lead to ASD. In
the study described here, we used Cul3 mouse models to evaluate the consequences
of Cul3 mutations in vivo. Our results show that Cul3 heterozygous knockout mice
exhibit deficits in motor coordination as well as ASD-relevant social and cognitive
impairments. Cul3+/-, Cul3+/fl Emx1-Cre and Cul3fl/fl Emx1-Cre mutant brains display
cortical lamination abnormalities due to defective migration of post-mitotic excitatory
neurons, as well as reduced numbers of excitatory and inhibitory neurons. In line
with the observed abnormal cortical organization, Cul3 heterozygous deletion is
associated with decreased spontaneous excitatory and inhibitory activity in the
cortex. At the molecular level we show that Cul3 regulates cytoskeletal and adhesion
protein abundance in the mouse embryonic cortex. Abnormal regulation of cytoskeletal
proteins in Cul3 mutant neural cells results in atypical organization of the actin
mesh at the cell leading edge. Of note, heterozygous deletion of Cul3 in adult
mice does not induce the majority of the behavioral defects observed in constitutive
Cul3 haploinsufficient animals, pointing to a critical time-window for Cul3 deficiency.\r\nIn
conclusion, our data indicate that Cul3 plays a critical role in the regulation
of cytoskeletal proteins and neuronal migration. ASD-associated defects and behavioral
abnormalities are primarily due to dosage sensitive Cul3 functions at early brain
developmental stages."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: I would like to especially thank Armel Nicolas from the Proteomics
and Christoph Sommer from the Bioimaging Facilities for the data analysis, and to
thank the team of the Preclinical Facility, especially Sabina Deixler, Angela Schlerka,
Anita Lepold, Mihalea Mihai and Michael Schun for taking care of the mouse line
maintenance and their great support.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
citation:
ama: Morandell J. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis.
2020. doi:10.15479/AT:ISTA:8620
apa: Morandell, J. (2020). Illuminating the role of Cul3 in autism spectrum disorder
pathogenesis. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8620
chicago: Morandell, Jasmin. “Illuminating the Role of Cul3 in Autism Spectrum Disorder
Pathogenesis.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8620.
ieee: J. Morandell, “Illuminating the role of Cul3 in autism spectrum disorder pathogenesis,”
Institute of Science and Technology Austria, 2020.
ista: Morandell J. 2020. Illuminating the role of Cul3 in autism spectrum disorder
pathogenesis. Institute of Science and Technology Austria.
mla: Morandell, Jasmin. Illuminating the Role of Cul3 in Autism Spectrum Disorder
Pathogenesis. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8620.
short: J. Morandell, Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis,
Institute of Science and Technology Austria, 2020.
date_created: 2020-10-07T14:53:13Z
date_published: 2020-10-12T00:00:00Z
date_updated: 2024-09-10T12:04:25Z
day: '12'
ddc:
- '610'
degree_awarded: PhD
department:
- _id: GaNo
doi: 10.15479/AT:ISTA:8620
file:
- access_level: open_access
checksum: 7ee83e42de3e5ce2fedb44dff472f75f
content_type: application/pdf
creator: jmorande
date_created: 2020-10-07T14:41:49Z
date_updated: 2021-10-16T22:30:04Z
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has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '138'
project:
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F07807
name: Neural stem cells in autism and epilepsy
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7800'
relation: part_of_dissertation
status: public
- id: '8131'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
title: Illuminating the role of Cul3 in autism spectrum disorder pathogenesis
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '8978'
abstract:
- lang: eng
text: "Mosaic analysis with double markers (MADM) technology enables concomitant
fluorescent cell labeling and induction of uniparental chromosome disomy (UPD)
with single-cell resolution. In UPD, imprinted genes are either overexpressed
2-fold or are not expressed. Here, the MADM platform is utilized to probe imprinting
phenotypes at the transcriptional level. This protocol highlights major steps
for the generation and isolation of projection neurons and astrocytes with MADM-induced
UPD from mouse cerebral cortex for downstream single-cell and low-input sample
RNA-sequencing experiments.\r\n\r\nFor complete details on the use and execution
of this protocol, please refer to Laukoter et al. (2020b)."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: This research was supported by the Scientific Service Units (SSU)
at IST Austria through resources provided by the Bioimaging (BIF) and Preclinical
Facilities (PCF). N.A received support from the FWF Firnberg-Programm (T 1031).
This work was also supported by IST Austria institutional funds; FWF SFB F78 to
S.H.; NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) to S.H.;
the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework
Programme (FP7/2007-2013) under REA grant agreement no. 618444 to S.H.; and the
European Research Council (ERC) under the European Union’s Horizon 2020 research
and innovation programme (grant agreement no. 725780 LinPro) to S.H.
article_number: '100215'
article_processing_charge: No
article_type: original
author:
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Laukoter S, Amberg N, Pauler F, Hippenmeyer S. Generation and isolation of
single cells from mouse brain with mosaic analysis with double markers-induced
uniparental chromosome disomy. STAR Protocols. 2020;1(3). doi:10.1016/j.xpro.2020.100215
apa: Laukoter, S., Amberg, N., Pauler, F., & Hippenmeyer, S. (2020). Generation
and isolation of single cells from mouse brain with mosaic analysis with double
markers-induced uniparental chromosome disomy. STAR Protocols. Elsevier.
https://doi.org/10.1016/j.xpro.2020.100215
chicago: Laukoter, Susanne, Nicole Amberg, Florian Pauler, and Simon Hippenmeyer.
“Generation and Isolation of Single Cells from Mouse Brain with Mosaic Analysis
with Double Markers-Induced Uniparental Chromosome Disomy.” STAR Protocols.
Elsevier, 2020. https://doi.org/10.1016/j.xpro.2020.100215.
ieee: S. Laukoter, N. Amberg, F. Pauler, and S. Hippenmeyer, “Generation and isolation
of single cells from mouse brain with mosaic analysis with double markers-induced
uniparental chromosome disomy,” STAR Protocols, vol. 1, no. 3. Elsevier,
2020.
ista: Laukoter S, Amberg N, Pauler F, Hippenmeyer S. 2020. Generation and isolation
of single cells from mouse brain with mosaic analysis with double markers-induced
uniparental chromosome disomy. STAR Protocols. 1(3), 100215.
mla: Laukoter, Susanne, et al. “Generation and Isolation of Single Cells from Mouse
Brain with Mosaic Analysis with Double Markers-Induced Uniparental Chromosome
Disomy.” STAR Protocols, vol. 1, no. 3, 100215, Elsevier, 2020, doi:10.1016/j.xpro.2020.100215.
short: S. Laukoter, N. Amberg, F. Pauler, S. Hippenmeyer, STAR Protocols 1 (2020).
date_created: 2020-12-30T10:17:07Z
date_published: 2020-12-18T00:00:00Z
date_updated: 2021-01-12T08:21:36Z
day: '18'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.xpro.2020.100215
ec_funded: 1
external_id:
pmid:
- '33377108'
file:
- access_level: open_access
checksum: f1e9a433e9cb0f41f7b6df6b76db1f6e
content_type: application/pdf
creator: dernst
date_created: 2021-01-07T15:57:27Z
date_updated: 2021-01-07T15:57:27Z
file_id: '8996'
file_name: 2020_STARProtocols_Laukoter.pdf
file_size: 4031449
relation: main_file
success: 1
file_date_updated: 2021-01-07T15:57:27Z
has_accepted_license: '1'
intvolume: ' 1'
issue: '3'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: STAR Protocols
publication_identifier:
issn:
- 2666-1667
publication_status: published
publisher: Elsevier
quality_controlled: '1'
status: public
title: Generation and isolation of single cells from mouse brain with mosaic analysis
with double markers-induced uniparental chromosome disomy
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2020'
...
---
_id: '7253'
abstract:
- lang: eng
text: The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted
Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex
development. How Cdkn1c regulates corticogenesis is however not clear. To this
end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically
dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find
that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous
one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous
Cdkn1c function which at the mechanistic level mediates radial glial progenitor
cell and nascent projection neuron survival. Strikingly, the growth-promoting
function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting.
Collectively, our results suggest that the Cdkn1c locus regulates cortical development
through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally,
our study highlights the importance to probe the relative contributions of cell
intrinsic gene function and tissue-wide mechanisms to the overall phenotype.
acknowledged_ssus:
- _id: PreCl
article_number: '195'
article_processing_charge: No
article_type: original
author:
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Keiichi I.
full_name: Nakayama, Keiichi I.
last_name: Nakayama
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. Imprinted
Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex
development. Nature Communications. 2020;11. doi:10.1038/s41467-019-14077-2
apa: Laukoter, S., Beattie, R. J., Pauler, F., Amberg, N., Nakayama, K. I., &
Hippenmeyer, S. (2020). Imprinted Cdkn1c genomic locus cell-autonomously promotes
cell survival in cerebral cortex development. Nature Communications. Springer
Nature. https://doi.org/10.1038/s41467-019-14077-2
chicago: Laukoter, Susanne, Robert J Beattie, Florian Pauler, Nicole Amberg, Keiichi
I. Nakayama, and Simon Hippenmeyer. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously
Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications.
Springer Nature, 2020. https://doi.org/10.1038/s41467-019-14077-2.
ieee: S. Laukoter, R. J. Beattie, F. Pauler, N. Amberg, K. I. Nakayama, and S. Hippenmeyer,
“Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral
cortex development,” Nature Communications, vol. 11. Springer Nature, 2020.
ista: Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. 2020.
Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral
cortex development. Nature Communications. 11, 195.
mla: Laukoter, Susanne, et al. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously
Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications,
vol. 11, 195, Springer Nature, 2020, doi:10.1038/s41467-019-14077-2.
short: S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer,
Nature Communications 11 (2020).
date_created: 2020-01-11T10:42:48Z
date_published: 2020-01-10T00:00:00Z
date_updated: 2023-08-17T14:23:41Z
day: '10'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41467-019-14077-2
ec_funded: 1
external_id:
isi:
- '000551459000005'
file:
- access_level: open_access
checksum: ebf1ed522f4e0be8d94c939c1806a709
content_type: application/pdf
creator: dernst
date_created: 2020-01-13T07:42:31Z
date_updated: 2020-07-14T12:47:54Z
file_id: '7261'
file_name: 2020_NatureComm_Laukoter.pdf
file_size: 8063333
relation: main_file
file_date_updated: 2020-07-14T12:47:54Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
project:
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/new-function-for-potential-tumour-suppressor-in-brain-development/
scopus_import: '1'
status: public
title: Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in
cerebral cortex development
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2020'
...
---
_id: '6849'
abstract:
- lang: eng
text: 'Brain function is mediated by complex dynamical interactions between excitatory
and inhibitory cell types. The Cholecystokinin-expressing inhibitory cells (CCK-interneurons)
are one of the least studied types, despite being suspected to play important
roles in cognitive processes. We studied the network effects of optogenetic silencing
of CCK-interneurons in the CA1 hippocampal area during exploration and sleep states.
The cell firing pattern in response to light pulses allowed us to classify the
recorded neurons in 5 classes, including disinhibited and non-responsive pyramidal
cell and interneurons, and the inhibited interneurons corresponding to the CCK
group. The light application, which inhibited the activity of CCK interneurons
triggered wider changes in the firing dynamics of cells. We observed rate changes
(i.e. remapping) of pyramidal cells during the exploration session in which the
light was applied relative to the previous control session that was not restricted
neither in time nor space to the light delivery. Also, the disinhibited pyramidal
cells had higher increase in bursting than in single spike firing rate as a result
of CCK silencing. In addition, the firing activity patterns during exploratory
periods were more weakly reactivated in sleep for those periods in which CCK-interneuron
were silenced than in the unaffected periods. Furthermore, light pulses during
sleep disrupted the reactivation of recent waking patterns. Hence, silencing CCK
neurons during exploration suppressed the reactivation of waking firing patterns
in sleep and CCK interneuron activity was also required during sleep for the normal
reactivation of waking patterns. These findings demonstrate the involvement of
CCK cells in reactivation-related memory consolidation. An important part of our
analysis was to test the relationship of the identified CCKinterneurons to brain
oscillations. Our findings showed that these cells exhibited different oscillatory
behaviour during anaesthesia and natural waking and sleep conditions. We showed
that: 1) Contrary to the past studies performed under anaesthesia, the identified
CCKinterneurons fired on the descending portion of the theta phase in waking exploration.
2) CCKinterneuron preferred phases around the trough of gamma oscillations. 3)
Contrary to anaesthesia conditions, the average firing rate of the CCK-interneurons
increased around the peak activity of the sharp-wave ripple (SWR) events in natural
sleep, which is congruent with new reports about their functional connectivity.
We also found that light driven CCK-interneuron silencing altered the dynamics
on the CA1 network oscillatory activity: 1) Pyramidal cells negatively shifted
their preferred theta phases when the light was applied, while interneurons responses
were less consistent. 2) As a population, pyramidal cells negatively shifted their
preferred activity during gamma oscillations, albeit we did not find gamma modulation
differences related to the light application when pyramidal cells were subdivided
into the disinhibited and unaffected groups. 3) During the peak of SWR events,
all but the CCK-interneurons had a reduction in their relative firing rate change
during the light application as compared to the change observed at SWR initiation.
Finally, regarding to the place field activity of the recorded pyramidal neurons,
we showed that the disinhibited pyramidal cells had reduced place field similarity,
coherence and spatial information, but only during the light application. The
mechanisms behind such observed behaviours might involve eCB signalling and plastic
changes in CCK-interneuron synapses. In conclusion, the observed changes related
to the light-mediated silencing of CCKinterneurons have unravelled characteristics
of this interneuron subpopulation that might change the understanding not only
of their particular network interactions, but also of the current theories about
the emergence of certain cognitive processes such as place coding needed for navigation
or hippocampus-dependent memory consolidation. '
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: M-Shop
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Dámaris K
full_name: Rangel Guerrero, Dámaris K
id: 4871BCE6-F248-11E8-B48F-1D18A9856A87
last_name: Rangel Guerrero
orcid: 0000-0002-8602-4374
citation:
ama: Rangel Guerrero DK. The role of CCK-interneurons in regulating hippocampal
network dynamics. 2019. doi:10.15479/AT:ISTA:6849
apa: Rangel Guerrero, D. K. (2019). The role of CCK-interneurons in regulating
hippocampal network dynamics. Institute of Science and Technology Austria.
https://doi.org/10.15479/AT:ISTA:6849
chicago: Rangel Guerrero, Dámaris K. “The Role of CCK-Interneurons in Regulating
Hippocampal Network Dynamics.” Institute of Science and Technology Austria, 2019.
https://doi.org/10.15479/AT:ISTA:6849.
ieee: D. K. Rangel Guerrero, “The role of CCK-interneurons in regulating hippocampal
network dynamics,” Institute of Science and Technology Austria, 2019.
ista: Rangel Guerrero DK. 2019. The role of CCK-interneurons in regulating hippocampal
network dynamics. Institute of Science and Technology Austria.
mla: Rangel Guerrero, Dámaris K. The Role of CCK-Interneurons in Regulating Hippocampal
Network Dynamics. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6849.
short: D.K. Rangel Guerrero, The Role of CCK-Interneurons in Regulating Hippocampal
Network Dynamics, Institute of Science and Technology Austria, 2019.
date_created: 2019-09-06T06:54:16Z
date_published: 2019-09-09T00:00:00Z
date_updated: 2023-09-19T10:01:12Z
day: '09'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: JoCs
doi: 10.15479/AT:ISTA:6849
file:
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checksum: 244dc4f74dbfc94f414156092298831f
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: drangel
date_created: 2019-09-09T13:09:45Z
date_updated: 2021-02-10T23:30:09Z
embargo_to: open_access
file_id: '6865'
file_name: Thesis_Damaris_Rangel_source.docx
file_size: 18253100
relation: source_file
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checksum: 59c73be40eeaa1c4db24067270151555
content_type: application/pdf
creator: drangel
date_created: 2019-09-09T13:09:52Z
date_updated: 2020-09-11T22:30:04Z
embargo: 2020-09-10
file_id: '6866'
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relation: main_file
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file_date_updated: 2021-02-10T23:30:09Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '97'
publication_identifier:
isbn:
- '9783990780039'
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '5914'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Jozsef L
full_name: Csicsvari, Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
title: The role of CCK-interneurons in regulating hippocampal network dynamics
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...
---
_id: '6947'
abstract:
- lang: eng
text: Lymph nodes are es s ential organs of the immune s ys tem where adaptive
immune responses originate, and consist of various leukocyte populations and a
stromal backbone. Fibroblastic reticular cells (FRCs) are the main stromal cells
and form a sponge-like extracellular matrix network, called conduits , which they thems
elves enwrap and contract. Lymph, containing s oluble antigens , arrive
in lymph nodes via afferent lymphatic vessels that connect to the s ubcaps
ular s inus and conduit network. According to the current paradigm, the conduit network dis
tributes afferent lymph through lymph nodes and thus provides acces
s for immune cells to lymph-borne antigens. An elas tic caps ule s urrounds the organ and confines the
immune cells and FRC network. Lymph nodes are completely packed with lymphocytes and lymphocyte numbers directly dictates the
size of the organ. Although lymphocytes cons tantly enter and leave the lymph node, its s
ize remains remarkedly s table under homeostatic conditions. It is only
partly known how the cellularity and s ize of the lymph node is regulated and how the lymph node is
able to swell in inflammation. The role of the FRC network in lymph node s
welling and trans fer of fluids are inves tigated in this thes is. Furthermore, we s
tudied what trafficking routes are us ed by cancer cells in lymph nodes to form distal
metastases.We examined the role of a mechanical feedback in regulation of lymph node
swelling. Using parallel plate compression and UV-las er cutting experiments we dis
s ected the mechanical force dynamics of the whole lymph node, and individually
for FRCs and the caps ule. Physical forces generated by packed lymphocytes directly affect the tens
ion on the FRC network and capsule, which increases its resistance to swelling. This implies a feedback mechanism between tis
s ue pres s ure and ability of lymphocytes to enter the organ. Following inflammation, the lymph node swells
∼10 fold in two weeks . Yet, what is the role for tens ion on the FRC network and caps
ule, and how are lymphocytes able to enter in conditions that resist
swelling remain open ques tions . We s how that tens ion on the FRC network is important
to limit the swelling rate of the organ so that the FRC network can grow in a coordinated fashion.
This is illustrated by interfering with FRC contractility, which leads to faster
swelling rates and a dis organized FRC network in the inflamed lymph node.
Growth of the FRC network in turn is expected to releas e tens ion on thes
e s tructures and lowers the res is tance to swelling, thereby allowing
more lymphocytes to enter the organ and drive more swelling. Halt of swelling
coincides with a thickening of the caps ule, which forms a thick res
is tant band around the organ and lowers tens ion on the FRC network to form
a new force equilibrium.The FRC and conduit network are further believed to be a privileged s
ite of s oluble information within the lymph node, although many details remain uns
olved. We s how by 3D ultra-recons truction that FRCs and antigen pres
enting cells cover the s urface of conduit s ys tem for more than 99%
and we dis cus s the implications for s oluble information exchangeat the conduit
level.Finally, there is an ongoing debate in the cancer field whether and how
cancer cells in lymph nodes s eed dis tal metas tas es . We s how that cancer cells infus
ed into the lymph node can utilize trafficking routes of immune cells and rapidly migrate to blood vessels.
Once in the blood circulation, these cells are able to form metastases in
distal tissues.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Frank P
full_name: Assen, Frank P
id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
last_name: Assen
orcid: 0000-0003-3470-6119
citation:
ama: 'Assen FP. Lymph node mechanics: Deciphering the interplay between stroma contractility,
morphology and lymphocyte trafficking. 2019. doi:10.15479/AT:ISTA:6947'
apa: 'Assen, F. P. (2019). Lymph node mechanics: Deciphering the interplay between
stroma contractility, morphology and lymphocyte trafficking. Institute of
Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6947'
chicago: 'Assen, Frank P. “Lymph Node Mechanics: Deciphering the Interplay between
Stroma Contractility, Morphology and Lymphocyte Trafficking.” Institute of Science
and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6947.'
ieee: 'F. P. Assen, “Lymph node mechanics: Deciphering the interplay between stroma
contractility, morphology and lymphocyte trafficking,” Institute of Science and
Technology Austria, 2019.'
ista: 'Assen FP. 2019. Lymph node mechanics: Deciphering the interplay between stroma
contractility, morphology and lymphocyte trafficking. Institute of Science and
Technology Austria.'
mla: 'Assen, Frank P. Lymph Node Mechanics: Deciphering the Interplay between
Stroma Contractility, Morphology and Lymphocyte Trafficking. Institute of
Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6947.'
short: 'F.P. Assen, Lymph Node Mechanics: Deciphering the Interplay between Stroma
Contractility, Morphology and Lymphocyte Trafficking, Institute of Science and
Technology Austria, 2019.'
date_created: 2019-10-14T16:54:52Z
date_published: 2019-10-09T00:00:00Z
date_updated: 2023-09-13T08:50:57Z
day: '9'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
doi: 10.15479/AT:ISTA:6947
file:
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checksum: 53a739752a500f84d0f8ec953cbbd0b6
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: fassen
date_created: 2019-11-06T12:30:02Z
date_updated: 2020-11-07T23:30:03Z
embargo_to: open_access
file_id: '6990'
file_name: PhDthesis_FrankAssen_revised2.docx
file_size: 214172667
relation: source_file
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checksum: 8c156b65d9347bb599623a4b09f15d15
content_type: application/pdf
creator: fassen
date_created: 2019-11-06T12:30:57Z
date_updated: 2020-11-07T23:30:03Z
embargo: 2020-11-06
file_id: '6991'
file_name: PhDthesis_FrankAssen_revised2.pdf
file_size: 83637532
relation: main_file
file_date_updated: 2020-11-07T23:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '142'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '664'
relation: part_of_dissertation
status: public
- id: '402'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
title: 'Lymph node mechanics: Deciphering the interplay between stroma contractility,
morphology and lymphocyte trafficking'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...
---
_id: '7001'
acknowledged_ssus:
- _id: PreCl
- _id: Bio
article_processing_charge: No
article_type: original
author:
- first_name: Cornelia
full_name: Schwayer, Cornelia
id: 3436488C-F248-11E8-B48F-1D18A9856A87
last_name: Schwayer
orcid: 0000-0001-5130-2226
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- first_name: Kornelija
full_name: Pranjic-Ferscha, Kornelija
id: 4362B3C2-F248-11E8-B48F-1D18A9856A87
last_name: Pranjic-Ferscha
- first_name: Alexandra
full_name: Schauer, Alexandra
id: 30A536BA-F248-11E8-B48F-1D18A9856A87
last_name: Schauer
orcid: 0000-0001-7659-9142
- first_name: M
full_name: Balda, M
last_name: Balda
- first_name: M
full_name: Tada, M
last_name: Tada
- first_name: K
full_name: Matter, K
last_name: Matter
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Schwayer C, Shamipour S, Pranjic-Ferscha K, et al. Mechanosensation of tight
junctions depends on ZO-1 phase separation and flow. Cell. 2019;179(4):937-952.e18.
doi:10.1016/j.cell.2019.10.006
apa: Schwayer, C., Shamipour, S., Pranjic-Ferscha, K., Schauer, A., Balda, M., Tada,
M., … Heisenberg, C.-P. J. (2019). Mechanosensation of tight junctions depends
on ZO-1 phase separation and flow. Cell. Cell Press. https://doi.org/10.1016/j.cell.2019.10.006
chicago: Schwayer, Cornelia, Shayan Shamipour, Kornelija Pranjic-Ferscha, Alexandra
Schauer, M Balda, M Tada, K Matter, and Carl-Philipp J Heisenberg. “Mechanosensation
of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” Cell. Cell
Press, 2019. https://doi.org/10.1016/j.cell.2019.10.006.
ieee: C. Schwayer et al., “Mechanosensation of tight junctions depends on
ZO-1 phase separation and flow,” Cell, vol. 179, no. 4. Cell Press, p.
937–952.e18, 2019.
ista: Schwayer C, Shamipour S, Pranjic-Ferscha K, Schauer A, Balda M, Tada M, Matter
K, Heisenberg C-PJ. 2019. Mechanosensation of tight junctions depends on ZO-1
phase separation and flow. Cell. 179(4), 937–952.e18.
mla: Schwayer, Cornelia, et al. “Mechanosensation of Tight Junctions Depends on
ZO-1 Phase Separation and Flow.” Cell, vol. 179, no. 4, Cell Press, 2019,
p. 937–952.e18, doi:10.1016/j.cell.2019.10.006.
short: C. Schwayer, S. Shamipour, K. Pranjic-Ferscha, A. Schauer, M. Balda, M. Tada,
K. Matter, C.-P.J. Heisenberg, Cell 179 (2019) 937–952.e18.
date_created: 2019-11-12T12:51:06Z
date_published: 2019-10-31T00:00:00Z
date_updated: 2024-03-25T23:30:21Z
day: '31'
ddc:
- '570'
department:
- _id: CaHe
- _id: BjHo
doi: 10.1016/j.cell.2019.10.006
ec_funded: 1
external_id:
isi:
- '000493898000012'
pmid:
- '31675500'
file:
- access_level: open_access
checksum: 33dac4bb77ee630e2666e936b4d57980
content_type: application/pdf
creator: dernst
date_created: 2020-10-21T07:09:45Z
date_updated: 2020-10-21T07:09:45Z
file_id: '8684'
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file_size: 8805878
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file_date_updated: 2020-10-21T07:09:45Z
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intvolume: ' 179'
isi: 1
issue: '4'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Submitted Version
page: 937-952.e18
pmid: 1
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742573'
name: Interaction and feedback between cell mechanics and fate specification in
vertebrate gastrulation
publication: Cell
publication_identifier:
eissn:
- 1097-4172
issn:
- 0092-8674
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
link:
- description: News auf IST Website
relation: press_release
url: https://ist.ac.at/en/news/biochemistry-meets-mechanics-the-sensitive-nature-of-cell-cell-contact-formation-in-embryo-development/
record:
- id: '7186'
relation: dissertation_contains
status: public
- id: '8350'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Mechanosensation of tight junctions depends on ZO-1 phase separation and flow
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 179
year: '2019'
...
---
_id: '6508'
abstract:
- lang: eng
text: Segregation of maternal determinants within the oocyte constitutes the first
step in embryo patterning. In zebrafish oocytes, extensive ooplasmic streaming
leads to the segregation of ooplasm from yolk granules along the animal-vegetal
axis of the oocyte. Here, we show that this process does not rely on cortical
actin reorganization, as previously thought, but instead on a cell-cycle-dependent
bulk actin polymerization wave traveling from the animal to the vegetal pole of
the oocyte. This wave functions in segregation by both pulling ooplasm animally
and pushing yolk granules vegetally. Using biophysical experimentation and theory,
we show that ooplasm pulling is mediated by bulk actin network flows exerting
friction forces on the ooplasm, while yolk granule pushing is achieved by a mechanism
closely resembling actin comet formation on yolk granules. Our study defines a
novel role of cell-cycle-controlled bulk actin polymerization waves in oocyte
polarization via ooplasmic segregation.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We would like to thank Pierre Recho, Guillaume Salbreux, and Silvia
Grigolon for advice on the theory, Lila Solnica-Krezel for kindly providing us with
zebrafish dachsous mutants, members of the Heisenberg and Hannezo groups for fruitful
discussions, and the Bioimaging and zebrafish facilities at IST Austria for their
continuous support. This project has received funding from the European Union (European
Research Council Advanced Grant 742573 to C.P.H.) and from the Austrian Science
Fund (FWF) (P 31639 to E.H.).
article_processing_charge: No
article_type: original
author:
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- first_name: Roland
full_name: Kardos, Roland
id: 4039350E-F248-11E8-B48F-1D18A9856A87
last_name: Kardos
- first_name: Shi-lei
full_name: Xue, Shi-lei
id: 31D2C804-F248-11E8-B48F-1D18A9856A87
last_name: Xue
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Shamipour S, Kardos R, Xue S, Hof B, Hannezo EB, Heisenberg C-PJ. Bulk actin
dynamics drive phase segregation in zebrafish oocytes. Cell. 2019;177(6):1463-1479.e18.
doi:10.1016/j.cell.2019.04.030
apa: Shamipour, S., Kardos, R., Xue, S., Hof, B., Hannezo, E. B., & Heisenberg,
C.-P. J. (2019). Bulk actin dynamics drive phase segregation in zebrafish oocytes.
Cell. Elsevier. https://doi.org/10.1016/j.cell.2019.04.030
chicago: Shamipour, Shayan, Roland Kardos, Shi-lei Xue, Björn Hof, Edouard B Hannezo,
and Carl-Philipp J Heisenberg. “Bulk Actin Dynamics Drive Phase Segregation in
Zebrafish Oocytes.” Cell. Elsevier, 2019. https://doi.org/10.1016/j.cell.2019.04.030.
ieee: S. Shamipour, R. Kardos, S. Xue, B. Hof, E. B. Hannezo, and C.-P. J. Heisenberg,
“Bulk actin dynamics drive phase segregation in zebrafish oocytes,” Cell,
vol. 177, no. 6. Elsevier, p. 1463–1479.e18, 2019.
ista: Shamipour S, Kardos R, Xue S, Hof B, Hannezo EB, Heisenberg C-PJ. 2019. Bulk
actin dynamics drive phase segregation in zebrafish oocytes. Cell. 177(6), 1463–1479.e18.
mla: Shamipour, Shayan, et al. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish
Oocytes.” Cell, vol. 177, no. 6, Elsevier, 2019, p. 1463–1479.e18, doi:10.1016/j.cell.2019.04.030.
short: S. Shamipour, R. Kardos, S. Xue, B. Hof, E.B. Hannezo, C.-P.J. Heisenberg,
Cell 177 (2019) 1463–1479.e18.
date_created: 2019-06-02T21:59:12Z
date_published: 2019-05-30T00:00:00Z
date_updated: 2024-03-25T23:30:21Z
day: '30'
ddc:
- '570'
department:
- _id: CaHe
- _id: EdHa
- _id: BjHo
doi: 10.1016/j.cell.2019.04.030
ec_funded: 1
external_id:
isi:
- '000469415100013'
pmid:
- '31080065'
file:
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checksum: aea43726d80e35ce3885073a5f05c3e3
content_type: application/pdf
creator: dernst
date_created: 2020-10-21T07:22:34Z
date_updated: 2020-10-21T07:22:34Z
file_id: '8686'
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file_size: 3356292
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success: 1
file_date_updated: 2020-10-21T07:22:34Z
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isi: 1
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language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.cell.2019.04.030
month: '05'
oa: 1
oa_version: Published Version
page: 1463-1479.e18
pmid: 1
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742573'
name: Interaction and feedback between cell mechanics and fate specification in
vertebrate gastrulation
- _id: 268294B6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P31639
name: Active mechano-chemical description of the cell cytoskeleton
publication: Cell
publication_identifier:
eissn:
- '10974172'
issn:
- '00928674'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/how-the-cytoplasm-separates-from-the-yolk/
record:
- id: '8350'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Bulk actin dynamics drive phase segregation in zebrafish oocytes
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 177
year: '2019'
...
---
_id: '3'
abstract:
- lang: eng
text: SETD5 gene mutations have been identified as a frequent cause of idiopathic
intellectual disability. Here we show that Setd5-haploinsufficient mice present
developmental defects such as abnormal brain-to-body weight ratios and neural
crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments
in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile
of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are
accompanied by abnormal expression of postsynaptic density proteins previously
associated with cognition. Our data additionally indicate that Setd5 regulates
RNA polymerase II dynamics and gene transcription via its interaction with the
Hdac3 and Paf1 complexes, findings potentially explaining the gene expression
defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive
role of Setd5 in a biological pathway found to be disrupted in humans with intellectual
disability and autism spectrum disorder.
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
acknowledgement: This work was supported by the Simons Foundation Autism Research
Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N.
article_processing_charge: No
article_type: original
author:
- first_name: Elena
full_name: Deliu, Elena
id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
last_name: Deliu
orcid: 0000-0002-7370-5293
- first_name: Niccoló
full_name: Arecco, Niccoló
last_name: Arecco
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Charles
full_name: Girardot, Charles
last_name: Girardot
- first_name: Eva
full_name: Käsper, Eva
last_name: Käsper
- first_name: Alena
full_name: Kozlova, Alena
id: C50A9596-02D0-11E9-976E-E38CFE5CBC1D
last_name: Kozlova
- first_name: Kasumi
full_name: Kishi, Kasumi
id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
last_name: Kishi
- first_name: Ilaria
full_name: Chiaradia, Ilaria
id: B6467F20-02D0-11E9-BDA5-E960C241894A
last_name: Chiaradia
orcid: 0000-0002-9529-4464
- first_name: Kyung
full_name: Noh, Kyung
last_name: Noh
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual
disability gene SETD5 disturbs developmental gene expression and cognition. Nature
Neuroscience. 2018;21(12):1717-1727. doi:10.1038/s41593-018-0266-2
apa: Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot,
C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene
SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience.
Nature Publishing Group. https://doi.org/10.1038/s41593-018-0266-2
chicago: Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena
Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual
Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature
Neuroscience. Nature Publishing Group, 2018. https://doi.org/10.1038/s41593-018-0266-2.
ieee: E. Deliu et al., “Haploinsufficiency of the intellectual disability
gene SETD5 disturbs developmental gene expression and cognition,” Nature Neuroscience,
vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018.
ista: Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper
E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition. Nature Neuroscience. 21(12), 1717–1727.
mla: Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene
SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience,
vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:10.1038/s41593-018-0266-2.
short: E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot,
E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience
21 (2018) 1717–1727.
date_created: 2018-12-11T11:44:05Z
date_published: 2018-11-19T00:00:00Z
date_updated: 2024-03-25T23:30:25Z
day: '19'
ddc:
- '570'
department:
- _id: GaNo
- _id: EdHa
doi: 10.1038/s41593-018-0266-2
external_id:
isi:
- '000451324700010'
file:
- access_level: open_access
checksum: 60abd0f05b7cdc08a6b0ec460884084f
content_type: application/pdf
creator: dernst
date_created: 2019-04-09T07:41:57Z
date_updated: 2020-07-14T12:45:58Z
file_id: '6255'
file_name: 2017_NatureNeuroscience_Deliu.pdf
file_size: 8167169
relation: main_file
file_date_updated: 2020-07-14T12:45:58Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '12'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Submitted Version
page: 1717 - 1727
project:
- _id: 254BA948-B435-11E9-9278-68D0E5697425
grant_number: '401299'
name: Probing development and reversibility of autism spectrum disorders
publication: Nature Neuroscience
publication_status: published
publisher: Nature Publishing Group
publist_id: '8054'
pubrep_id: '1071'
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/
record:
- id: '6074'
relation: popular_science
status: public
- id: '12364'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental
gene expression and cognition
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 21
year: '2018'
...
---
_id: '323'
abstract:
- lang: eng
text: 'In the here presented thesis, we explore the role of branched actin networks
in cell migration and antigen presentation, the two most relevant processes in
dendritic cell biology. Branched actin networks construct lamellipodial protrusions
at the leading edge of migrating cells. These are typically seen as adhesive structures,
which mediate force transduction to the extracellular matrix that leads to forward
locomotion. We ablated Arp2/3 nucleation promoting factor WAVE in DCs and found
that the resulting cells lack lamellipodial protrusions. Instead, depending on
the maturation state, one or multiple filopodia were formed. By challenging these
cells in a variety of migration assays we found that lamellipodial protrusions
are dispensable for the locomotion of leukocytes and actually dampen the speed
of migration. However, lamellipodia are critically required to negotiate complex
environments that DCs experience while they travel to the next draining lymph
node. Taken together our results suggest that leukocyte lamellipodia have rather
a sensory- than a force transducing function. Furthermore, we show for the first
time structure and dynamics of dendritic cell F-actin at the immunological synapse
with naïve T cells. Dendritic cell F-actin appears as dynamic foci that are nucleated
by the Arp2/3 complex. WAVE ablated dendritic cells show increased membrane tension,
leading to an altered ultrastructure of the immunological synapse and severe T
cell priming defects. These results point towards a previously unappreciated role
of the cellular mechanics of dendritic cells in T cell activation. Additionally,
we present a novel cell culture based system for the differentiation of dendritic
cells from conditionally immortalized hematopoietic precursors. These precursor
cells are genetically tractable via the CRISPR/Cas9 system while they retain their
ability to differentiate into highly migratory dendritic cells and other immune
cells. This will foster the study of all aspects of dendritic cell biology and
beyond. '
acknowledged_ssus:
- _id: NanoFab
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: "First of all I would like to thank Michael Sixt for giving me the
opportunity to work in \r\nhis group and for his support throughout the years. He
is a truly inspiring person and \r\nthe best boss one can imagine. I would
\ also like to thank all current and past \r\nmembers of the Sixt group for
their help and the great working atmosphere in the lab. \r\nIt is a true privilege
to work with such a bright, funny and friendly group of people and \r\nI’m proud
\ that I could be part of it. Furthermore, I would like to say ‘thank
\ you’ to Daria Siekhaus for all the meetings and discussion we had throughout
the years \r\nand to Federica Benvenuti for being part of my committee.
\ I am also grateful to Jack \r\nMerrin in the nanofabrication facility
\ and all the people working in the bioimaging-\r\n, the electron microscopy-
and the preclinical facilities."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
citation:
ama: Leithner AF. Branched actin networks in dendritic cell biology. 2018. doi:10.15479/AT:ISTA:th_998
apa: Leithner, A. F. (2018). Branched actin networks in dendritic cell biology.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_998
chicago: Leithner, Alexander F. “Branched Actin Networks in Dendritic Cell Biology.”
Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_998.
ieee: A. F. Leithner, “Branched actin networks in dendritic cell biology,” Institute
of Science and Technology Austria, 2018.
ista: Leithner AF. 2018. Branched actin networks in dendritic cell biology. Institute
of Science and Technology Austria.
mla: Leithner, Alexander F. Branched Actin Networks in Dendritic Cell Biology.
Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_998.
short: A.F. Leithner, Branched Actin Networks in Dendritic Cell Biology, Institute
of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:45:49Z
date_published: 2018-04-12T00:00:00Z
date_updated: 2023-09-07T12:39:44Z
day: '12'
ddc:
- '571'
- '599'
- '610'
degree_awarded: PhD
department:
- _id: MiSi
doi: 10.15479/AT:ISTA:th_998
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creator: dernst
date_created: 2019-04-05T09:23:11Z
date_updated: 2021-02-11T11:17:16Z
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file_date_updated: 2021-02-11T23:30:17Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: '99'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7542'
pubrep_id: '998'
related_material:
record:
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relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
title: Branched actin networks in dendritic cell biology
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...
---
_id: '395'
abstract:
- lang: eng
text: 'Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping
with other neurological conditions. Despite the remarkable number of scientific
breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders
(e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great
challenge. Recent advancements in geno mics, like whole-exome or whole-genome
sequencing, have enabled scientists to identify numerous mutations underlying
neurodevelopmental disorders. Given the few hundred risk genes that were discovered,
the etiological variability and the heterogeneous phenotypic outcomes, the need
for genotype -along with phenotype- based diagnosis of individual patients becomes
a requisite. Driven by this rationale, in a previous study our group described
mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding
for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause
of ASD. Following up on the role of BCAAs, in the study described here we show
that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter
localized mainly at the blood brain barrier (BBB), has an essential role in maintaining
normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial
cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation
and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from
the neural progenitor cell population leads to microcephaly. Interestingly, we
demonstrate that BCAA intracerebroventricular administration ameliorates abnormal
behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients
diagnosed with neurological dis o r ders helped us identify several patients with
autistic traits, microcephaly and motor delay carrying deleterious homozygous
mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological
syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA
s in human bra in function. Together with r ecent studies (described in chapter
two) that have successfully made the transition into clinical practice, our findings
on the role of B CAAs might have a crucial impact on the development of novel
individualized therapeutic strategies for ASD. '
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Dora-Clara
full_name: Tarlungeanu, Dora-Clara
id: 2ABCE612-F248-11E8-B48F-1D18A9856A87
last_name: Tarlungeanu
citation:
ama: Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders
. 2018. doi:10.15479/AT:ISTA:th_992
apa: Tarlungeanu, D.-C. (2018). The branched chain amino acids in autism spectrum
disorders . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_992
chicago: Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum
Disorders .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_992.
ieee: D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders
,” Institute of Science and Technology Austria, 2018.
ista: Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders
. Institute of Science and Technology Austria.
mla: Tarlungeanu, Dora-Clara. The Branched Chain Amino Acids in Autism Spectrum
Disorders . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_992.
short: D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders
, Institute of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:46:14Z
date_published: 2018-03-01T00:00:00Z
date_updated: 2023-09-07T12:38:59Z
day: '01'
ddc:
- '570'
- '616'
degree_awarded: PhD
department:
- _id: GaNo
doi: 10.15479/AT:ISTA:th_992
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date_created: 2019-04-05T09:19:17Z
date_updated: 2021-02-11T23:30:15Z
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date_created: 2019-04-05T09:19:17Z
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file_date_updated: 2021-02-11T23:30:15Z
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '88'
project:
- _id: 25473368-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: F03523
name: Transmembrane Transporters in Health and Disease
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7434'
pubrep_id: '992'
related_material:
record:
- id: '1183'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
title: 'The branched chain amino acids in autism spectrum disorders '
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...