---
_id: '10301'
abstract:
- lang: eng
text: De novo protein synthesis is required for synapse modifications underlying
stable memory encoding. Yet neurons are highly compartmentalized cells and how
protein synthesis can be regulated at the synapse level is unknown. Here, we characterize
neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic
target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to
mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A
subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR
complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR
activation and restricts the mTOR-dependent translation of specific activity-regulated
mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent
protein synthesis, and facilitates the consolidation of associative and spatial
memories in mice. The memory enhancement becomes evident with light or spaced
training, can be achieved by selectively deleting GluN3A from excitatory neurons
during adulthood, and does not compromise other aspects of cognition such as memory
flexibility or extinction. Our findings provide mechanistic insight into synaptic
translational control and reveal a potentially selective target for cognitive
enhancement.
acknowledgement: We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a
knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral
and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and
Ana Navarro for expert technical help. Work was funded by the UTE project CIMA;
fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO
(to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.),
FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.);
ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program
RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077
FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637)
and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator
Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R),
Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence
Awards (SEV-2013-0317, SEV-2017-0723).
article_number: e71575
article_processing_charge: No
article_type: original
author:
- first_name: María J
full_name: Conde-Dusman, María J
last_name: Conde-Dusman
- first_name: Partha N
full_name: Dey, Partha N
last_name: Dey
- first_name: Óscar
full_name: Elía-Zudaire, Óscar
last_name: Elía-Zudaire
- first_name: Luis E
full_name: Garcia Rabaneda, Luis E
id: 33D1B084-F248-11E8-B48F-1D18A9856A87
last_name: Garcia Rabaneda
- first_name: Carmen
full_name: García-Lira, Carmen
last_name: García-Lira
- first_name: Teddy
full_name: Grand, Teddy
last_name: Grand
- first_name: Victor
full_name: Briz, Victor
last_name: Briz
- first_name: Eric R
full_name: Velasco, Eric R
last_name: Velasco
- first_name: Raül
full_name: Andero Galí, Raül
last_name: Andero Galí
- first_name: Sergio
full_name: Niñerola, Sergio
last_name: Niñerola
- first_name: Angel
full_name: Barco, Angel
last_name: Barco
- first_name: Pierre
full_name: Paoletti, Pierre
last_name: Paoletti
- first_name: John F
full_name: Wesseling, John F
last_name: Wesseling
- first_name: Fabrizio
full_name: Gardoni, Fabrizio
last_name: Gardoni
- first_name: Steven J
full_name: Tavalin, Steven J
last_name: Tavalin
- first_name: Isabel
full_name: Perez-Otaño, Isabel
last_name: Perez-Otaño
citation:
ama: Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis
and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly.
eLife. 2021;10. doi:10.7554/elife.71575
apa: Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E.,
García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis
and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly.
ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.71575
chicago: Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia
Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein
Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1
Assembly.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.71575.
ieee: M. J. Conde-Dusman et al., “Control of protein synthesis and memory
by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” eLife,
vol. 10. eLife Sciences Publications, 2021.
ista: Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C,
Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling
JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and
memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife.
10, e71575.
mla: Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by
GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife,
vol. 10, e71575, eLife Sciences Publications, 2021, doi:10.7554/elife.71575.
short: M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira,
T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti,
J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021).
date_created: 2021-11-18T06:59:45Z
date_published: 2021-11-17T00:00:00Z
date_updated: 2023-08-14T11:50:50Z
day: '17'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.7554/elife.71575
external_id:
isi:
- '000720945900001'
file:
- access_level: open_access
checksum: 59318e9e41507cec83c2f4070e6ad540
content_type: application/pdf
creator: lgarciar
date_created: 2021-11-18T07:02:02Z
date_updated: 2021-11-18T07:02:02Z
file_id: '10302'
file_name: elife-71575-v1.pdf
file_size: 2477302
relation: main_file
success: 1
file_date_updated: 2021-11-18T07:02:02Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
keyword:
- general immunology and microbiology
- general biochemistry
- genetics and molecular biology
- general medicine
- general neuroscience
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
status: public
title: Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition
of GIT1/mTORC1 assembly
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: 10
year: '2021'
...
---
_id: '9953'
abstract:
- lang: eng
text: Chronic psychological stress is one of the most important triggers and environmental
risk factors for neuropsychiatric disorders. Chronic stress can influence all
organs via the secretion of stress hormones, including glucocorticoids by the
adrenal glands, which coordinate the stress response across the body. In the brain,
glucocorticoid receptors (GR) are expressed by various cell types including microglia,
which are its resident immune cells regulating stress-induced inflammatory processes.
To study the roles of microglial GR under normal homeostatic conditions and following
chronic stress, we generated a mouse model in which the GR gene is depleted in
microglia specifically at adulthood to prevent developmental confounds. We first
confirmed that microglia were depleted in GR in our model in males and females
among the cingulate cortex and the hippocampus, both stress-sensitive brain regions.
Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were
housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable
mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR
depleted and WT animals as demonstrated by a decrease of both saccharine preference
and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and
neural mechanisms underlying the adaptation to stress occurred differently between
the two genotypes. Upon CUMS exposure, microglial morphology was altered in the
WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore,
in the standard environment condition, GR depleted-microglia showed increased
expression of pro-inflammatory genes, and genes involved in microglial homeostatic
functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition,
GR depleted-microglia showed reduced expression levels of pro-inflammatory genes
and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia.
Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant
reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences
in adult hippocampal neurogenesis were observed between the genotypes during normal
homeostatic conditions, with microglial-GR deficiency increasing the formation
of newborn neurons in the dentate gyrus subgranular zone independently from stress
exposure. Together, these findings indicate that, although the deletion of microglial
GR did not prevent the animal’s ability to respond to stress, it contributed to
modulating hippocampal functions in both standard and stressful conditions, notably
by shaping the microglial response to chronic stress.
acknowledgement: We acknowledge that Université Laval stands on the traditional and
unceded land of the Huron-Wendat peoples; and that the University of Victoria exists
on the territory of the Lekwungen peoples and that the Songhees, Esquimalt and WSÁNEÆ
peoples have relationships to this land. We thank Emmanuel Planel for the access
to the epifluorescence microscope and Julie-Christine Lévesque at the Bioimaging
Platform of CRCHU de Québec-Université Laval for technical assistance. We also thank
the Centre for Advanced Materials and Related Technology for the access to the confocal
microscope with Airyscan. K.P. was supported by a doctoral scholarship from Fonds
de Recherche du Québec – Santé (FRQS), an excellence award from Fondation du CHU
de Québec, as well as from Centre Thématique de Recherche en Neurosciences and from
Fondation Famille-Choquette. K.B. was supported by excellence scholarships from
Université Laval and Fondation du CHU de Québec. S.G. is supported by FIRC-AIRC
fellowship for Italy 22329/2018 and by Pilot ARISLA NKINALS 2019. C.W.H. and J.C.S.
were supported by postdoctoral fellowships from FRQS. This study was funded by a
Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant
(RGPIN-2014-05308) awarded to M.E.T., by ERANET neuron 2017 MicroSynDep to M.E.T.
and I.B., and by the Italian Ministry of Health, grant RF-2018-12367249 to I.B,
by PRIN 2017, AIRC 2019 and Ministero della Salute RF2018 to C.L. M.E.T. is a Tier
II Canada Research Chair in Neurobiology of Aging and Cognition.
article_processing_charge: No
article_type: original
author:
- first_name: Katherine
full_name: Picard, Katherine
last_name: Picard
- first_name: Kanchan
full_name: Bisht, Kanchan
last_name: Bisht
- first_name: Silvia
full_name: Poggini, Silvia
last_name: Poggini
- first_name: Stefano
full_name: Garofalo, Stefano
last_name: Garofalo
- first_name: Maria Teresa
full_name: Golia, Maria Teresa
last_name: Golia
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Fatima
full_name: Abdallah, Fatima
last_name: Abdallah
- first_name: Naomi
full_name: Ciano Albanese, Naomi
last_name: Ciano Albanese
- first_name: Irmgard
full_name: Amrein, Irmgard
last_name: Amrein
- first_name: Nathalie
full_name: Vernoux, Nathalie
last_name: Vernoux
- first_name: Kaushik
full_name: Sharma, Kaushik
last_name: Sharma
- first_name: Chin Wai
full_name: Hui, Chin Wai
last_name: Hui
- first_name: Julie
full_name: C. Savage, Julie
last_name: C. Savage
- first_name: Cristina
full_name: Limatola, Cristina
last_name: Limatola
- first_name: Davide
full_name: Ragozzino, Davide
last_name: Ragozzino
- first_name: Laura
full_name: Maggi, Laura
last_name: Maggi
- first_name: Igor
full_name: Branchi, Igor
last_name: Branchi
- first_name: Marie Ève
full_name: Tremblay, Marie Ève
last_name: Tremblay
citation:
ama: Picard K, Bisht K, Poggini S, et al. Microglial-glucocorticoid receptor depletion
alters the response of hippocampal microglia and neurons in a chronic unpredictable
mild stress paradigm in female mice. Brain, Behavior, and Immunity. 2021;97:423-439.
doi:10.1016/j.bbi.2021.07.022
apa: Picard, K., Bisht, K., Poggini, S., Garofalo, S., Golia, M. T., Basilico, B.,
… Tremblay, M. È. (2021). Microglial-glucocorticoid receptor depletion alters
the response of hippocampal microglia and neurons in a chronic unpredictable mild
stress paradigm in female mice. Brain, Behavior, and Immunity. Elsevier.
https://doi.org/10.1016/j.bbi.2021.07.022
chicago: Picard, Katherine, Kanchan Bisht, Silvia Poggini, Stefano Garofalo, Maria
Teresa Golia, Bernadette Basilico, Fatima Abdallah, et al. “Microglial-Glucocorticoid
Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in
a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” Brain, Behavior,
and Immunity. Elsevier, 2021. https://doi.org/10.1016/j.bbi.2021.07.022.
ieee: K. Picard et al., “Microglial-glucocorticoid receptor depletion alters
the response of hippocampal microglia and neurons in a chronic unpredictable mild
stress paradigm in female mice,” Brain, Behavior, and Immunity, vol. 97.
Elsevier, pp. 423–439, 2021.
ista: Picard K, Bisht K, Poggini S, Garofalo S, Golia MT, Basilico B, Abdallah F,
Ciano Albanese N, Amrein I, Vernoux N, Sharma K, Hui CW, C. Savage J, Limatola
C, Ragozzino D, Maggi L, Branchi I, Tremblay MÈ. 2021. Microglial-glucocorticoid
receptor depletion alters the response of hippocampal microglia and neurons in
a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior,
and Immunity. 97, 423–439.
mla: Picard, Katherine, et al. “Microglial-Glucocorticoid Receptor Depletion Alters
the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild
Stress Paradigm in Female Mice.” Brain, Behavior, and Immunity, vol. 97,
Elsevier, 2021, pp. 423–39, doi:10.1016/j.bbi.2021.07.022.
short: K. Picard, K. Bisht, S. Poggini, S. Garofalo, M.T. Golia, B. Basilico, F.
Abdallah, N. Ciano Albanese, I. Amrein, N. Vernoux, K. Sharma, C.W. Hui, J. C.
Savage, C. Limatola, D. Ragozzino, L. Maggi, I. Branchi, M.È. Tremblay, Brain,
Behavior, and Immunity 97 (2021) 423–439.
date_created: 2021-08-22T22:01:21Z
date_published: 2021-10-01T00:00:00Z
date_updated: 2023-10-03T09:49:18Z
day: '01'
department:
- _id: GaNo
doi: 10.1016/j.bbi.2021.07.022
external_id:
isi:
- '000702878400007'
pmid:
- '34343616'
intvolume: ' 97'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.zora.uzh.ch/id/eprint/208855/1/ZORA208855.pdf
month: '10'
oa: 1
oa_version: Submitted Version
page: 423-439
pmid: 1
publication: Brain, Behavior, and Immunity
publication_identifier:
issn:
- 0889-1591
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microglial-glucocorticoid receptor depletion alters the response of hippocampal
microglia and neurons in a chronic unpredictable mild stress paradigm in female
mice
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 97
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: '7877'
abstract:
- lang: eng
text: The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations inNIPBLaccount
for most cases ofthe rare developmental disorder Cornelia de Lange syndrome (CdLS).
Here we report aMAU2 variant causing CdLS, a deletion of seven amino acids that
impairs the interaction between MAU2 and the NIPBL N terminus.Investigating this
interaction, we discovered that MAU2 and the NIPBL N terminus are largely dispensable
fornormal cohesin and NIPBL function in cells with a NIPBL early truncating mutation.
Despite a predicted fataloutcome of an out-of-frame single nucleotide duplication
inNIPBL, engineered in two different cell lines,alternative translation initiation
yields a form of NIPBL missing N-terminal residues. This form cannot interactwith
MAU2, but binds DNA and mediates cohesin loading. Altogether, our work reveals
that cohesin loading can occur independently of functional NIPBL/MAU2 complexes
and highlights a novel mechanism protectiveagainst out-of-frame mutations that
is potentially relevant for other genetic conditions.
article_number: '107647'
article_processing_charge: No
article_type: original
author:
- first_name: Ilaria
full_name: Parenti, Ilaria
id: D93538B0-5B71-11E9-AC62-02EBE5697425
last_name: Parenti
- first_name: Farah
full_name: Diab, Farah
last_name: Diab
- first_name: Sara Ruiz
full_name: Gil, Sara Ruiz
last_name: Gil
- first_name: Eskeatnaf
full_name: Mulugeta, Eskeatnaf
last_name: Mulugeta
- first_name: Valentina
full_name: Casa, Valentina
last_name: Casa
- first_name: Riccardo
full_name: Berutti, Riccardo
last_name: Berutti
- first_name: Rutger W.W.
full_name: Brouwer, Rutger W.W.
last_name: Brouwer
- first_name: Valerie
full_name: Dupé, Valerie
last_name: Dupé
- first_name: Juliane
full_name: Eckhold, Juliane
last_name: Eckhold
- first_name: Elisabeth
full_name: Graf, Elisabeth
last_name: Graf
- first_name: Beatriz
full_name: Puisac, Beatriz
last_name: Puisac
- first_name: Feliciano
full_name: Ramos, Feliciano
last_name: Ramos
- first_name: Thomas
full_name: Schwarzmayr, Thomas
last_name: Schwarzmayr
- first_name: Macarena Moronta
full_name: Gines, Macarena Moronta
last_name: Gines
- first_name: Thomas
full_name: Van Staveren, Thomas
last_name: Van Staveren
- first_name: Wilfred F.J.
full_name: Van Ijcken, Wilfred F.J.
last_name: Van Ijcken
- first_name: Tim M.
full_name: Strom, Tim M.
last_name: Strom
- first_name: Juan
full_name: Pié, Juan
last_name: Pié
- first_name: Erwan
full_name: Watrin, Erwan
last_name: Watrin
- first_name: Frank J.
full_name: Kaiser, Frank J.
last_name: Kaiser
- first_name: Kerstin S.
full_name: Wendt, Kerstin S.
last_name: Wendt
citation:
ama: Parenti I, Diab F, Gil SR, et al. MAU2 and NIPBL variants impair the heterodimerization
of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports.
2020;31(7). doi:10.1016/j.celrep.2020.107647
apa: Parenti, I., Diab, F., Gil, S. R., Mulugeta, E., Casa, V., Berutti, R., … Wendt,
K. S. (2020). MAU2 and NIPBL variants impair the heterodimerization of the cohesin
loader subunits and cause Cornelia de Lange syndrome. Cell Reports. Elsevier.
https://doi.org/10.1016/j.celrep.2020.107647
chicago: Parenti, Ilaria, Farah Diab, Sara Ruiz Gil, Eskeatnaf Mulugeta, Valentina
Casa, Riccardo Berutti, Rutger W.W. Brouwer, et al. “MAU2 and NIPBL Variants Impair
the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange
Syndrome.” Cell Reports. Elsevier, 2020. https://doi.org/10.1016/j.celrep.2020.107647.
ieee: I. Parenti et al., “MAU2 and NIPBL variants impair the heterodimerization
of the cohesin loader subunits and cause Cornelia de Lange syndrome,” Cell
Reports, vol. 31, no. 7. Elsevier, 2020.
ista: Parenti I, Diab F, Gil SR, Mulugeta E, Casa V, Berutti R, Brouwer RWW, Dupé
V, Eckhold J, Graf E, Puisac B, Ramos F, Schwarzmayr T, Gines MM, Van Staveren
T, Van Ijcken WFJ, Strom TM, Pié J, Watrin E, Kaiser FJ, Wendt KS. 2020. MAU2
and NIPBL variants impair the heterodimerization of the cohesin loader subunits
and cause Cornelia de Lange syndrome. Cell Reports. 31(7), 107647.
mla: Parenti, Ilaria, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization
of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell
Reports, vol. 31, no. 7, 107647, Elsevier, 2020, doi:10.1016/j.celrep.2020.107647.
short: I. Parenti, F. Diab, S.R. Gil, E. Mulugeta, V. Casa, R. Berutti, R.W.W. Brouwer,
V. Dupé, J. Eckhold, E. Graf, B. Puisac, F. Ramos, T. Schwarzmayr, M.M. Gines,
T. Van Staveren, W.F.J. Van Ijcken, T.M. Strom, J. Pié, E. Watrin, F.J. Kaiser,
K.S. Wendt, Cell Reports 31 (2020).
date_created: 2020-05-24T22:00:57Z
date_published: 2020-05-19T00:00:00Z
date_updated: 2023-08-21T06:27:47Z
day: '19'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1016/j.celrep.2020.107647
external_id:
isi:
- '000535655200005'
file:
- access_level: open_access
checksum: 64d8f7467731ee5c166b10b939b8310b
content_type: application/pdf
creator: dernst
date_created: 2020-05-26T11:05:01Z
date_updated: 2020-07-14T12:48:04Z
file_id: '7892'
file_name: 2020_CellReports_Parenti.pdf
file_size: 4695682
relation: main_file
file_date_updated: 2020-07-14T12:48:04Z
has_accepted_license: '1'
intvolume: ' 31'
isi: 1
issue: '7'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
publication: Cell Reports
publication_identifier:
eissn:
- '22111247'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader
subunits and cause Cornelia de Lange syndrome
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: 31
year: '2020'
...
---
_id: '7957'
abstract:
- lang: eng
text: "Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain
development and function and are characterized by wide genetic and clinical variability.
In this review, we discuss the multiple factors that influence the clinical presentation
of NDDs, with particular attention to gene vulnerability, mutational load, and
the two-hit model. Despite the complex architecture of\r\nmutational events associated
with NDDs, the various proteins involved appear to converge on common pathways,
such as synaptic plasticity/function, chromatin remodelers and the mammalian target
of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind
these pathways will hopefully lead to the identification of candidates that could
be targeted for treatment approaches."
acknowledgement: We wish to thank Jasmin Morandell for generously sharing Figure 2.
This work was supported by the European Research Council Starting Grant (grant 715508
) to G.N.
article_processing_charge: No
article_type: original
author:
- first_name: Ilaria
full_name: Parenti, Ilaria
id: D93538B0-5B71-11E9-AC62-02EBE5697425
last_name: Parenti
- first_name: Luis E
full_name: Garcia Rabaneda, Luis E
id: 33D1B084-F248-11E8-B48F-1D18A9856A87
last_name: Garcia Rabaneda
- first_name: Hanna
full_name: Schön, Hanna
id: C8E17EDC-D7AA-11E9-B7B7-45ECE5697425
last_name: Schön
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: 'Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. Neurodevelopmental disorders:
From genetics to functional pathways. Trends in Neurosciences. 2020;43(8):608-621.
doi:10.1016/j.tins.2020.05.004'
apa: 'Parenti, I., Garcia Rabaneda, L. E., Schön, H., & Novarino, G. (2020).
Neurodevelopmental disorders: From genetics to functional pathways. Trends
in Neurosciences. Elsevier. https://doi.org/10.1016/j.tins.2020.05.004'
chicago: 'Parenti, Ilaria, Luis E Garcia Rabaneda, Hanna Schön, and Gaia Novarino.
“Neurodevelopmental Disorders: From Genetics to Functional Pathways.” Trends
in Neurosciences. Elsevier, 2020. https://doi.org/10.1016/j.tins.2020.05.004.'
ieee: 'I. Parenti, L. E. Garcia Rabaneda, H. Schön, and G. Novarino, “Neurodevelopmental
disorders: From genetics to functional pathways,” Trends in Neurosciences,
vol. 43, no. 8. Elsevier, pp. 608–621, 2020.'
ista: 'Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. 2020. Neurodevelopmental
disorders: From genetics to functional pathways. Trends in Neurosciences. 43(8),
608–621.'
mla: 'Parenti, Ilaria, et al. “Neurodevelopmental Disorders: From Genetics to Functional
Pathways.” Trends in Neurosciences, vol. 43, no. 8, Elsevier, 2020, pp.
608–21, doi:10.1016/j.tins.2020.05.004.'
short: I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences
43 (2020) 608–621.
date_created: 2020-06-14T22:00:49Z
date_published: 2020-08-01T00:00:00Z
date_updated: 2023-08-21T08:25:31Z
day: '01'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1016/j.tins.2020.05.004
ec_funded: 1
external_id:
isi:
- '000553090600008'
pmid:
- '32507511'
file:
- access_level: open_access
checksum: 67db0251b1d415ae59005f876fcf9e34
content_type: application/pdf
creator: dernst
date_created: 2020-11-25T09:43:40Z
date_updated: 2020-11-25T09:43:40Z
file_id: '8805'
file_name: 2020_TrendsNeuroscience_Parenti.pdf
file_size: 1439550
relation: main_file
success: 1
file_date_updated: 2020-11-25T09:43:40Z
has_accepted_license: '1'
intvolume: ' 43'
isi: 1
issue: '8'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 608-621
pmid: 1
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
publication: Trends in Neurosciences
publication_identifier:
eissn:
- 1878108X
issn:
- '01662236'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Neurodevelopmental disorders: From genetics to functional pathways'
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: 43
year: '2020'
...
---
_id: '8131'
abstract:
- lang: eng
text: The possibility to generate construct valid animal models enabled the development
and testing of therapeutic strategies targeting the core features of autism spectrum
disorders (ASDs). At the same time, these studies highlighted the necessity of
identifying sensitive developmental time windows for successful therapeutic interventions.
Animal and human studies also uncovered the possibility to stratify the variety
of ASDs in molecularly distinct subgroups, potentially facilitating effective
treatment design. Here, we focus on the molecular pathways emerging as commonly
affected by mutations in diverse ASD-risk genes, on their role during critical
windows of brain development and the potential treatments targeting these biological
processes.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Basilico B, Morandell J, Novarino G. Molecular mechanisms for targeted ASD
treatments. Current Opinion in Genetics and Development. 2020;65(12):126-137.
doi:10.1016/j.gde.2020.06.004
apa: Basilico, B., Morandell, J., & Novarino, G. (2020). Molecular mechanisms
for targeted ASD treatments. Current Opinion in Genetics and Development.
Elsevier. https://doi.org/10.1016/j.gde.2020.06.004
chicago: Basilico, Bernadette, Jasmin Morandell, and Gaia Novarino. “Molecular Mechanisms
for Targeted ASD Treatments.” Current Opinion in Genetics and Development.
Elsevier, 2020. https://doi.org/10.1016/j.gde.2020.06.004.
ieee: B. Basilico, J. Morandell, and G. Novarino, “Molecular mechanisms for targeted
ASD treatments,” Current Opinion in Genetics and Development, vol. 65,
no. 12. Elsevier, pp. 126–137, 2020.
ista: Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted
ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137.
mla: Basilico, Bernadette, et al. “Molecular Mechanisms for Targeted ASD Treatments.”
Current Opinion in Genetics and Development, vol. 65, no. 12, Elsevier,
2020, pp. 126–37, doi:10.1016/j.gde.2020.06.004.
short: B. Basilico, J. Morandell, G. Novarino, Current Opinion in Genetics and Development
65 (2020) 126–137.
date_created: 2020-07-19T22:00:58Z
date_published: 2020-12-01T00:00:00Z
date_updated: 2024-09-10T12:04:25Z
day: '01'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1016/j.gde.2020.06.004
ec_funded: 1
external_id:
isi:
- '000598918900019'
pmid:
- '32659636'
file:
- access_level: open_access
content_type: application/pdf
creator: dernst
date_created: 2020-07-22T06:47:45Z
date_updated: 2020-07-22T06:47:45Z
file_id: '8146'
file_name: 2020_CurrentOpGenetics_Basilico.pdf
file_size: 1381545
relation: main_file
success: 1
file_date_updated: 2020-07-22T06:47:45Z
has_accepted_license: '1'
intvolume: ' 65'
isi: 1
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 126-137
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _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: Current Opinion in Genetics and Development
publication_identifier:
eissn:
- '18790380'
issn:
- 0959437X
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '8620'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Molecular mechanisms for targeted ASD treatments
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: 65
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
embargo: 2021-10-15
file_id: '8621'
file_name: Jasmin_Morandell_Thesis-2020_final.pdf
file_size: 16155786
relation: main_file
- access_level: closed
checksum: 5e0464af453734210ce7aab7b4a92e3a
content_type: application/x-zip-compressed
creator: jmorande
date_created: 2020-10-07T14:45:07Z
date_updated: 2021-10-16T22:30:04Z
embargo_to: open_access
file_id: '8622'
file_name: Jasmin_Morandell_Thesis-2020_final.zip
file_size: 24344152
relation: source_file
file_date_updated: 2021-10-16T22:30:04Z
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: '7149'
abstract:
- lang: eng
text: In recent years, many genes have been associated with chromatinopathies classified
as “Cornelia de Lange Syndrome‐like.” It is known that the phenotype of these
patients becomes less recognizable, overlapping to features characteristic of
other syndromes caused by genetic variants affecting different regulators of chromatin
structure and function. Therefore, Cornelia de Lange syndrome diagnosis might
be arduous due to the seldom discordance between unexpected molecular diagnosis
and clinical evaluation. Here, we review the molecular features of Cornelia de
Lange syndrome, supporting the hypothesis that “CdLS‐like syndromes” are part
of a larger “rare disease family” sharing multiple clinical features and common
disrupted molecular pathways.
acknowledgement: ' Dipartimento DiSS, Università degli Studi di Milano, Grant/Award
Number: Linea 2; Fondazione Cariplo, Grant/Award Number: 2015-0783; German Federal
Ministry of Education and Research (BMBF), Grant/Award Number: CHROMATIN-Net; Medical
Faculty of the University of Lübeck, Grant/Award Number: J09-2017; Nickel & Co S.p.A.;
Università degli Studi di Milano, Grant/Award Numbers: Molecular & Translational
Medicine PhD Scholarship, Translational Medicine PhD Scholarship'
article_processing_charge: No
article_type: review
author:
- first_name: Laura
full_name: Avagliano, Laura
last_name: Avagliano
- first_name: Ilaria
full_name: Parenti, Ilaria
id: D93538B0-5B71-11E9-AC62-02EBE5697425
last_name: Parenti
- first_name: Paolo
full_name: Grazioli, Paolo
last_name: Grazioli
- first_name: Elisabetta
full_name: Di Fede, Elisabetta
last_name: Di Fede
- first_name: Chiara
full_name: Parodi, Chiara
last_name: Parodi
- first_name: Milena
full_name: Mariani, Milena
last_name: Mariani
- first_name: Frank J.
full_name: Kaiser, Frank J.
last_name: Kaiser
- first_name: Angelo
full_name: Selicorni, Angelo
last_name: Selicorni
- first_name: Cristina
full_name: Gervasini, Cristina
last_name: Gervasini
- first_name: Valentina
full_name: Massa, Valentina
last_name: Massa
citation:
ama: 'Avagliano L, Parenti I, Grazioli P, et al. Chromatinopathies: A focus on Cornelia
de Lange syndrome. Clinical Genetics. 2020;97(1):3-11. doi:10.1111/cge.13674'
apa: 'Avagliano, L., Parenti, I., Grazioli, P., Di Fede, E., Parodi, C., Mariani,
M., … Massa, V. (2020). Chromatinopathies: A focus on Cornelia de Lange syndrome.
Clinical Genetics. Wiley. https://doi.org/10.1111/cge.13674'
chicago: 'Avagliano, Laura, Ilaria Parenti, Paolo Grazioli, Elisabetta Di Fede,
Chiara Parodi, Milena Mariani, Frank J. Kaiser, Angelo Selicorni, Cristina Gervasini,
and Valentina Massa. “Chromatinopathies: A Focus on Cornelia de Lange Syndrome.”
Clinical Genetics. Wiley, 2020. https://doi.org/10.1111/cge.13674.'
ieee: 'L. Avagliano et al., “Chromatinopathies: A focus on Cornelia de Lange
syndrome,” Clinical Genetics, vol. 97, no. 1. Wiley, pp. 3–11, 2020.'
ista: 'Avagliano L, Parenti I, Grazioli P, Di Fede E, Parodi C, Mariani M, Kaiser
FJ, Selicorni A, Gervasini C, Massa V. 2020. Chromatinopathies: A focus on Cornelia
de Lange syndrome. Clinical Genetics. 97(1), 3–11.'
mla: 'Avagliano, Laura, et al. “Chromatinopathies: A Focus on Cornelia de Lange
Syndrome.” Clinical Genetics, vol. 97, no. 1, Wiley, 2020, pp. 3–11, doi:10.1111/cge.13674.'
short: L. Avagliano, I. Parenti, P. Grazioli, E. Di Fede, C. Parodi, M. Mariani,
F.J. Kaiser, A. Selicorni, C. Gervasini, V. Massa, Clinical Genetics 97 (2020)
3–11.
date_created: 2019-12-04T16:10:59Z
date_published: 2020-01-01T00:00:00Z
date_updated: 2023-08-17T14:06:20Z
day: '01'
department:
- _id: GaNo
doi: 10.1111/cge.13674
external_id:
isi:
- '000562561800001'
pmid:
- '31721174'
intvolume: ' 97'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa_version: None
page: 3-11
pmid: 1
publication: Clinical Genetics
publication_identifier:
eissn:
- 1399-0004
issn:
- 0009-9163
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Chromatinopathies: A focus on Cornelia de Lange syndrome'
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 97
year: '2020'
...
---
_id: '7488'
abstract:
- lang: eng
text: Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is
associated with a recognisable facial pattern. However, the heterogeneity in causal
genes and the presence of overlapping syndromes have made it increasingly difficult
to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene,
is having a growing impact on the diagnosis and management of genetic diseases
by analysing the features of affected individuals. Here, we performed a phenotypic
study on a cohort of 49 individuals harbouring causative variants in known CdLS
genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis
of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within
the top five predicted syndromes for 97.9% of our cases and even listed as first
prediction for 83.7%. The age of patients did not seem to affect the prediction
accuracy, whereas our results indicate a correlation between the clinical score
and affected genes. Furthermore, each gene presents a different pattern recognition
that may be used to develop new neural networks with the goal of separating different
genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis
based on deep learning could support the clinical diagnosis of CdLS.
article_number: '1042'
article_processing_charge: No
article_type: original
author:
- first_name: Ana
full_name: Latorre-Pellicer, Ana
last_name: Latorre-Pellicer
- first_name: Ángela
full_name: Ascaso, Ángela
last_name: Ascaso
- first_name: Laura
full_name: Trujillano, Laura
last_name: Trujillano
- first_name: Marta
full_name: Gil-Salvador, Marta
last_name: Gil-Salvador
- first_name: Maria
full_name: Arnedo, Maria
last_name: Arnedo
- first_name: Cristina
full_name: Lucia-Campos, Cristina
last_name: Lucia-Campos
- first_name: Rebeca
full_name: Antoñanzas-Pérez, Rebeca
last_name: Antoñanzas-Pérez
- first_name: Iñigo
full_name: Marcos-Alcalde, Iñigo
last_name: Marcos-Alcalde
- first_name: Ilaria
full_name: Parenti, Ilaria
id: D93538B0-5B71-11E9-AC62-02EBE5697425
last_name: Parenti
- first_name: Gloria
full_name: Bueno-Lozano, Gloria
last_name: Bueno-Lozano
- first_name: Antonio
full_name: Musio, Antonio
last_name: Musio
- first_name: Beatriz
full_name: Puisac, Beatriz
last_name: Puisac
- first_name: Frank J.
full_name: Kaiser, Frank J.
last_name: Kaiser
- first_name: Feliciano J.
full_name: Ramos, Feliciano J.
last_name: Ramos
- first_name: Paulino
full_name: Gómez-Puertas, Paulino
last_name: Gómez-Puertas
- first_name: Juan
full_name: Pié, Juan
last_name: Pié
citation:
ama: Latorre-Pellicer A, Ascaso Á, Trujillano L, et al. Evaluating Face2Gene as
a tool to identify Cornelia de Lange syndrome by facial phenotypes. International
Journal of Molecular Sciences. 2020;21(3). doi:10.3390/ijms21031042
apa: Latorre-Pellicer, A., Ascaso, Á., Trujillano, L., Gil-Salvador, M., Arnedo,
M., Lucia-Campos, C., … Pié, J. (2020). Evaluating Face2Gene as a tool to identify
Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular
Sciences. MDPI. https://doi.org/10.3390/ijms21031042
chicago: Latorre-Pellicer, Ana, Ángela Ascaso, Laura Trujillano, Marta Gil-Salvador,
Maria Arnedo, Cristina Lucia-Campos, Rebeca Antoñanzas-Pérez, et al. “Evaluating
Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes.”
International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21031042.
ieee: A. Latorre-Pellicer et al., “Evaluating Face2Gene as a tool to identify
Cornelia de Lange syndrome by facial phenotypes,” International Journal of
Molecular Sciences, vol. 21, no. 3. MDPI, 2020.
ista: Latorre-Pellicer A, Ascaso Á, Trujillano L, Gil-Salvador M, Arnedo M, Lucia-Campos
C, Antoñanzas-Pérez R, Marcos-Alcalde I, Parenti I, Bueno-Lozano G, Musio A, Puisac
B, Kaiser FJ, Ramos FJ, Gómez-Puertas P, Pié J. 2020. Evaluating Face2Gene as
a tool to identify Cornelia de Lange syndrome by facial phenotypes. International
Journal of Molecular Sciences. 21(3), 1042.
mla: Latorre-Pellicer, Ana, et al. “Evaluating Face2Gene as a Tool to Identify Cornelia
de Lange Syndrome by Facial Phenotypes.” International Journal of Molecular
Sciences, vol. 21, no. 3, 1042, MDPI, 2020, doi:10.3390/ijms21031042.
short: A. Latorre-Pellicer, Á. Ascaso, L. Trujillano, M. Gil-Salvador, M. Arnedo,
C. Lucia-Campos, R. Antoñanzas-Pérez, I. Marcos-Alcalde, I. Parenti, G. Bueno-Lozano,
A. Musio, B. Puisac, F.J. Kaiser, F.J. Ramos, P. Gómez-Puertas, J. Pié, International
Journal of Molecular Sciences 21 (2020).
date_created: 2020-02-16T23:00:49Z
date_published: 2020-02-04T00:00:00Z
date_updated: 2023-08-18T06:35:41Z
day: '04'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3390/ijms21031042
external_id:
isi:
- '000522551606028'
file:
- access_level: open_access
checksum: 0e6658c4fe329d55d4d9bef01c5b15d0
content_type: application/pdf
creator: dernst
date_created: 2020-02-18T07:49:22Z
date_updated: 2020-07-14T12:47:59Z
file_id: '7496'
file_name: 2020_IntMolecSciences_Latorre.pdf
file_size: 4271234
relation: main_file
file_date_updated: 2020-07-14T12:47:59Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '3'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
publication: International Journal of Molecular Sciences
publication_identifier:
eissn:
- '14220067'
issn:
- '16616596'
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial
phenotypes
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: 21
year: '2020'
...
---
_id: '7586'
abstract:
- lang: eng
text: CLC chloride/proton exchangers may support acidification of endolysosomes
and raise their luminal Cl− concentration. Disruption of endosomal ClC‐3 causes
severe neurodegeneration. To assess the importance of ClC‐3 Cl−/H+ exchange, we
now generate Clcn3unc/unc mice in which ClC‐3 is converted into a Cl− channel.
Unlike Clcn3−/− mice, Clcn3unc/unc mice appear normal owing to compensation by
ClC‐4 with which ClC‐3 forms heteromers. ClC‐4 protein levels are strongly reduced
in Clcn3−/−, but not in Clcn3unc/unc mice because ClC‐3unc binds and stabilizes
ClC‐4 like wild‐type ClC‐3. Although mice lacking ClC‐4 appear healthy, its absence
in Clcn3unc/unc/Clcn4−/− mice entails even stronger neurodegeneration than observed
in Clcn3−/− mice. A fraction of ClC‐3 is found on synaptic vesicles, but miniature
postsynaptic currents and synaptic vesicle acidification are not affected in Clcn3unc/unc
or Clcn3−/− mice before neurodegeneration sets in. Both, Cl−/H+‐exchange activity
and the stabilizing effect on ClC‐4, are central to the biological function of
ClC‐3.
acknowledgement: "We thank T. Stauber and T. Breiderhoff for cloning expression constructs;
K. Räbel, S. Hohensee, and C. Backhaus for technical assistance; R. Jahn (MPIbpc,
Göttingen) for providing the equipment required for SV purification; and A\r\nWoehler
(MDC, Berlin) for assistance with SV imaging. Supported, in part, by grants from
the Deutsche Forschungsgemeinschaft (JE164/9-2, SFB740 TP C5, FOR 2625 (JE164/14-1),
NeuroCure Cluster of Excellence), the European Research Council Advanced Grant CYTOVOLION
(ERC 294435) and the Prix Louis-Jeantet de Médecine to TJJ, and Peter and Traudl
Engelhorn fellowship to ZF."
article_number: e103358
article_processing_charge: No
article_type: original
author:
- first_name: Stefanie
full_name: Weinert, Stefanie
last_name: Weinert
- first_name: Niclas
full_name: Gimber, Niclas
last_name: Gimber
- first_name: Dorothea
full_name: Deuschel, Dorothea
last_name: Deuschel
- first_name: Till
full_name: Stuhlmann, Till
last_name: Stuhlmann
- first_name: Dmytro
full_name: Puchkov, Dmytro
last_name: Puchkov
- first_name: Zohreh
full_name: Farsi, Zohreh
last_name: Farsi
- first_name: Carmen F.
full_name: Ludwig, Carmen F.
last_name: Ludwig
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Karen I.
full_name: López-Cayuqueo, Karen I.
last_name: López-Cayuqueo
- first_name: Rosa
full_name: Planells-Cases, Rosa
last_name: Planells-Cases
- first_name: Thomas J.
full_name: Jentsch, Thomas J.
last_name: Jentsch
citation:
ama: Weinert S, Gimber N, Deuschel D, et al. Uncoupling endosomal CLC chloride/proton
exchange causes severe neurodegeneration. EMBO Journal. 2020;39. doi:10.15252/embj.2019103358
apa: Weinert, S., Gimber, N., Deuschel, D., Stuhlmann, T., Puchkov, D., Farsi, Z.,
… Jentsch, T. J. (2020). Uncoupling endosomal CLC chloride/proton exchange causes
severe neurodegeneration. EMBO Journal. EMBO Press. https://doi.org/10.15252/embj.2019103358
chicago: Weinert, Stefanie, Niclas Gimber, Dorothea Deuschel, Till Stuhlmann, Dmytro
Puchkov, Zohreh Farsi, Carmen F. Ludwig, et al. “Uncoupling Endosomal CLC Chloride/Proton
Exchange Causes Severe Neurodegeneration.” EMBO Journal. EMBO Press, 2020.
https://doi.org/10.15252/embj.2019103358.
ieee: S. Weinert et al., “Uncoupling endosomal CLC chloride/proton exchange
causes severe neurodegeneration,” EMBO Journal, vol. 39. EMBO Press, 2020.
ista: Weinert S, Gimber N, Deuschel D, Stuhlmann T, Puchkov D, Farsi Z, Ludwig CF,
Novarino G, López-Cayuqueo KI, Planells-Cases R, Jentsch TJ. 2020. Uncoupling
endosomal CLC chloride/proton exchange causes severe neurodegeneration. EMBO Journal.
39, e103358.
mla: Weinert, Stefanie, et al. “Uncoupling Endosomal CLC Chloride/Proton Exchange
Causes Severe Neurodegeneration.” EMBO Journal, vol. 39, e103358, EMBO
Press, 2020, doi:10.15252/embj.2019103358.
short: S. Weinert, N. Gimber, D. Deuschel, T. Stuhlmann, D. Puchkov, Z. Farsi, C.F.
Ludwig, G. Novarino, K.I. López-Cayuqueo, R. Planells-Cases, T.J. Jentsch, EMBO
Journal 39 (2020).
date_created: 2020-03-15T23:00:55Z
date_published: 2020-03-02T00:00:00Z
date_updated: 2023-08-18T07:07:36Z
day: '02'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.15252/embj.2019103358
external_id:
isi:
- '000517335000001'
pmid:
- '32118314'
file:
- access_level: open_access
checksum: 82750a7a93e3740decbce8474004111a
content_type: application/pdf
creator: dernst
date_created: 2020-03-23T13:51:11Z
date_updated: 2020-07-14T12:48:00Z
file_id: '7615'
file_name: 2020_EMBO_Weinert.pdf
file_size: 12243278
relation: main_file
file_date_updated: 2020-07-14T12:48:00Z
has_accepted_license: '1'
intvolume: ' 39'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: EMBO Journal
publication_identifier:
eissn:
- '14602075'
issn:
- '02614189'
publication_status: published
publisher: EMBO Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration
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: 39
year: '2020'
...
---
_id: '6896'
abstract:
- lang: eng
text: "Until recently, a great amount of brain studies have been conducted in human
post mortem tissues, cell lines and model organisms. These researches provided
useful insights regarding cell-cell interactions occurring in the brain. However,
such approaches suffer from technical limitations and inaccurate modeling of the
tissue 3D cytoarchitecture. Importantly, they might lack a human genetic background
essential for disease modeling. With the development of protocols to generate
human cerebral organoids, we are now closer to reproducing the early stages of
human brain development in vitro. As a result, more relevant cell-cell interaction
studies can be conducted.\r\n\r\nIn this review, we discuss the advantages of
3D cultures over 2D in modulating brain cell-cell interactions during physiological
and pathological development, as well as the progress made in developing organoids
in which neurons, macroglia, microglia and vascularization are present. Finally,
we debate the limitations of those models and possible future directions."
article_number: '146458'
article_processing_charge: No
article_type: original
author:
- first_name: Bárbara
full_name: Oliveira, Bárbara
id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
last_name: Oliveira
- first_name: Aysan Çerağ
full_name: Yahya, Aysan Çerağ
id: 365A65F8-F248-11E8-B48F-1D18A9856A87
last_name: Yahya
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Oliveira B, Yahya AÇ, Novarino G. Modeling cell-cell interactions in the brain
using cerebral organoids. Brain Research. 2019;1724. doi:10.1016/j.brainres.2019.146458
apa: Oliveira, B., Yahya, A. Ç., & Novarino, G. (2019). Modeling cell-cell interactions
in the brain using cerebral organoids. Brain Research. Elsevier. https://doi.org/10.1016/j.brainres.2019.146458
chicago: Oliveira, Bárbara, Aysan Çerağ Yahya, and Gaia Novarino. “Modeling Cell-Cell
Interactions in the Brain Using Cerebral Organoids.” Brain Research. Elsevier,
2019. https://doi.org/10.1016/j.brainres.2019.146458.
ieee: B. Oliveira, A. Ç. Yahya, and G. Novarino, “Modeling cell-cell interactions
in the brain using cerebral organoids,” Brain Research, vol. 1724. Elsevier,
2019.
ista: Oliveira B, Yahya AÇ, Novarino G. 2019. Modeling cell-cell interactions in
the brain using cerebral organoids. Brain Research. 1724, 146458.
mla: Oliveira, Bárbara, et al. “Modeling Cell-Cell Interactions in the Brain Using
Cerebral Organoids.” Brain Research, vol. 1724, 146458, Elsevier, 2019,
doi:10.1016/j.brainres.2019.146458.
short: B. Oliveira, A.Ç. Yahya, G. Novarino, Brain Research 1724 (2019).
date_created: 2019-09-22T22:00:35Z
date_published: 2019-12-01T00:00:00Z
date_updated: 2023-08-30T06:19:49Z
day: '01'
department:
- _id: GaNo
doi: 10.1016/j.brainres.2019.146458
external_id:
isi:
- '000491646600033'
pmid:
- '31521639'
intvolume: ' 1724'
isi: 1
language:
- iso: eng
month: '12'
oa_version: None
pmid: 1
publication: Brain Research
publication_identifier:
eissn:
- '18726240'
issn:
- '00068993'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Modeling cell-cell interactions in the brain using cerebral organoids
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 1724
year: '2019'
...
---
_id: '7414'
article_processing_charge: No
article_type: original
author:
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Dora-Clara
full_name: Tarlungeanu, Dora-Clara
id: 2ABCE612-F248-11E8-B48F-1D18A9856A87
last_name: Tarlungeanu
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Knaus L, Tarlungeanu D-C, Novarino G. S.16.03 A homozygous missense mutation
in SLC7A5 leads to autism spectrum disorder and microcephaly. European Neuropsychopharmacology.
2019;29(Supplement 6):S11. doi:10.1016/j.euroneuro.2019.09.039
apa: Knaus, L., Tarlungeanu, D.-C., & Novarino, G. (2019). S.16.03 A homozygous
missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly.
European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.039
chicago: Knaus, Lisa, Dora-Clara Tarlungeanu, and Gaia Novarino. “S.16.03 A Homozygous
Missense Mutation in SLC7A5 Leads to Autism Spectrum Disorder and Microcephaly.”
European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.039.
ieee: L. Knaus, D.-C. Tarlungeanu, and G. Novarino, “S.16.03 A homozygous missense
mutation in SLC7A5 leads to autism spectrum disorder and microcephaly,” European
Neuropsychopharmacology, vol. 29, no. Supplement 6. Elsevier, p. S11, 2019.
ista: Knaus L, Tarlungeanu D-C, Novarino G. 2019. S.16.03 A homozygous missense
mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. European
Neuropsychopharmacology. 29(Supplement 6), S11.
mla: Knaus, Lisa, et al. “S.16.03 A Homozygous Missense Mutation in SLC7A5 Leads
to Autism Spectrum Disorder and Microcephaly.” European Neuropsychopharmacology,
vol. 29, no. Supplement 6, Elsevier, 2019, p. S11, doi:10.1016/j.euroneuro.2019.09.039.
short: L. Knaus, D.-C. Tarlungeanu, G. Novarino, European Neuropsychopharmacology
29 (2019) S11.
date_created: 2020-01-30T10:06:15Z
date_published: 2019-12-13T00:00:00Z
date_updated: 2023-09-07T14:55:23Z
day: '13'
department:
- _id: GaNo
doi: 10.1016/j.euroneuro.2019.09.039
external_id:
isi:
- '000502657500020'
intvolume: ' 29'
isi: 1
issue: Supplement 6
language:
- iso: eng
month: '12'
oa_version: None
page: S11
publication: European Neuropsychopharmacology
publication_identifier:
issn:
- 0924-977X
publication_status: published
publisher: Elsevier
quality_controlled: '1'
status: public
title: S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder
and microcephaly
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 29
year: '2019'
...
---
_id: '7415'
article_processing_charge: No
article_type: original
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- 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, Nicolas A, Schwarz LA, Novarino G. S.16.05 Illuminating the role
of the e3 ubiquitin ligase cullin3 in brain development and autism. European
Neuropsychopharmacology. 2019;29(Supplement 6):S11-S12. doi:10.1016/j.euroneuro.2019.09.040
apa: Morandell, J., Nicolas, A., Schwarz, L. A., & Novarino, G. (2019). S.16.05
Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development
and autism. European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.040
chicago: Morandell, Jasmin, Armel Nicolas, Lena A Schwarz, and Gaia Novarino. “S.16.05
Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development
and Autism.” European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.040.
ieee: J. Morandell, A. Nicolas, L. A. Schwarz, and G. Novarino, “S.16.05 Illuminating
the role of the e3 ubiquitin ligase cullin3 in brain development and autism,”
European Neuropsychopharmacology, vol. 29, no. Supplement 6. Elsevier,
pp. S11–S12, 2019.
ista: Morandell J, Nicolas A, Schwarz LA, Novarino G. 2019. S.16.05 Illuminating
the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European
Neuropsychopharmacology. 29(Supplement 6), S11–S12.
mla: Morandell, Jasmin, et al. “S.16.05 Illuminating the Role of the E3 Ubiquitin
Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology,
vol. 29, no. Supplement 6, Elsevier, 2019, pp. S11–12, doi:10.1016/j.euroneuro.2019.09.040.
short: J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology
29 (2019) S11–S12.
date_created: 2020-01-30T10:07:41Z
date_published: 2019-12-13T00:00:00Z
date_updated: 2023-09-07T14:56:17Z
day: '13'
department:
- _id: GaNo
- _id: LifeSc
doi: 10.1016/j.euroneuro.2019.09.040
external_id:
isi:
- '000502657500021'
intvolume: ' 29'
isi: 1
issue: Supplement 6
language:
- iso: eng
month: '12'
oa_version: None
page: S11-S12
publication: European Neuropsychopharmacology
publication_identifier:
issn:
- 0924-977X
publication_status: published
publisher: Elsevier
quality_controlled: '1'
status: public
title: S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development
and autism
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 29
year: '2019'
...
---
_id: '6074'
abstract:
- lang: eng
text: "This dataset contains the supplementary data for the research paper \"Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition\".\r\n\r\nThe contained files have the following content:\r\n'Supplementary
Figures.pdf'\r\n\tAdditional figures (as referenced in the paper).\r\n'Supplementary
Table 1. Statistics.xlsx'\r\n\tDetails on statistical tests performed in the paper.\r\n'Supplementary
Table 2. Differentially expressed gene analysis.xlsx'\r\n\tResults for the differential
gene expression analysis for embryonic (E9.5; analysis with edgeR) and in vitro
(ESCs, EBs, NPCs; analysis with DESeq2) samples.\r\n'Supplementary Table 3. Gene
Ontology (GO) term enrichment analysis.xlsx'\r\n\tResults for the GO term enrichment
analysis for differentially expressed genes in embryonic (GO E9.5) and in vitro
(GO ESC, GO EBs, GO NPCs) samples. Differentially expressed genes for in vitro
samples were split into upregulated and downregulated genes (up/down) and the
analysis was performed on each subset (e.g. GO ESC up / GO ESC down).\r\n'Supplementary
Table 4. Differentially expressed gene analysis for CFC samples.xlsx'\r\n\tResults
for the differential gene expression analysis for samples from adult mice before
(HC - Homecage) and 1h and 3h after contextual fear conditioning (1h and 3h, respectively).
Each sheet shows the results for a different comparison. Sheets 1-3 show results
for comparisons between timepoints for wild type (WT) samples only and sheets
4-6 for the same comparisons in mutant (Het) samples. Sheets 7-9 show results
for comparisons between genotypes at each time point and sheet 10 contains the
results for the analysis of differential expression trajectories between wild
type and mutant.\r\n'Supplementary Table 5. Cluster identification.xlsx'\r\n\tResults
for k-means clustering of genes by expression. Sheet 1 shows clustering of just
the genes with significantly different expression trajectories between genotypes.
Sheet 2 shows clustering of all genes that are significantly differentially expressed
in any of the comparisons (includes also genes with same trajectories).\r\n'Supplementary
Table 6. GO term cluster analysis.xlsx'\r\n\tResults for the GO term enrichment
analysis and EWCE analysis for enrichment of cell type specific genes for each
cluster identified by clustering genes with different expression trajectories
(see Table S5, sheet 1).\r\n'Supplementary Table 7. Setd5 mass spectrometry results.xlsx'\r\n\tResults
showing proteins interacting with Setd5 as identified by mass spectrometry. Sheet
1 shows protein protein interaction data generated from these results (combined
with data from the STRING database. Sheet 2 shows the results of the statistical
analysis with limma.\r\n'Supplementary Table 8. PolII ChIP-seq analysis.xlsx'\r\n\tResults
for the Chip-Seq analysis for binding of RNA polymerase II (PolII). Sheet 1 shows
results for differential binding of PolII at the transcription start site (TSS)
between genotypes and sheets 2+3 show the corresponding GO enrichment analysis
for these differentially bound genes. Sheet 4 shows RNAseq counts for genes with
increased binding of PolII at the TSS."
article_processing_charge: No
author:
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Dotter C, Novarino G. Supplementary data for the research paper “Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition.” 2019. doi:10.15479/AT:ISTA:6074
apa: Dotter, C., & Novarino, G. (2019). Supplementary data for the research
paper “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental
gene expression and cognition.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6074
chicago: Dotter, Christoph, and Gaia Novarino. “Supplementary Data for the Research
Paper ‘Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental
Gene Expression and Cognition.’” Institute of Science and Technology Austria,
2019. https://doi.org/10.15479/AT:ISTA:6074.
ieee: C. Dotter and G. Novarino, “Supplementary data for the research paper ‘Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition.’” Institute of Science and Technology Austria, 2019.
ista: Dotter C, Novarino G. 2019. Supplementary data for the research paper ‘Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:6074.
mla: Dotter, Christoph, and Gaia Novarino. Supplementary Data for the Research
Paper “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental
Gene Expression and Cognition.” Institute of Science and Technology Austria,
2019, doi:10.15479/AT:ISTA:6074.
short: C. Dotter, G. Novarino, (2019).
date_created: 2019-03-07T13:32:35Z
date_published: 2019-01-09T00:00:00Z
date_updated: 2024-02-21T13:41:01Z
day: '09'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.15479/AT:ISTA:6074
file:
- access_level: open_access
checksum: bc1b285edca9e98a2c63d153c79bb75b
content_type: application/zip
creator: dernst
date_created: 2019-03-07T13:37:19Z
date_updated: 2020-07-14T12:47:18Z
file_id: '6084'
file_name: Setd5_paper.zip
file_size: 33202743
relation: supplementary_material
file_date_updated: 2020-07-14T12:47:18Z
has_accepted_license: '1'
month: '01'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '3'
relation: research_paper
status: public
status: public
title: Supplementary data for the research paper "Haploinsufficiency of the intellectual
disability gene SETD5 disturbs developmental gene expression and cognition"
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
_id: '6088'
abstract:
- lang: eng
text: P-Glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two
efflux transporters at the blood–brain barrier (BBB), which effectively restrict
brain distribution of diverse drugs, such as tyrosine kinase inhibitors. There
is a crucial need for pharmacological ABCB1 and ABCG2 inhibition protocols for
a more effective treatment of brain diseases. In the present study, seven marketed
drugs (osimertinib, erlotinib, nilotinib, imatinib, lapatinib, pazopanib, and
cyclosporine A) and one nonmarketed drug (tariquidar), with known in vitro ABCB1/ABCG2
inhibitory properties, were screened for their inhibitory potency at the BBB in
vivo. Positron emission tomography (PET) using the model ABCB1/ABCG2 substrate
[11C]erlotinib was performed in mice. Tested inhibitors were administered as i.v.
bolus injections at 30 min before the start of the PET scan, followed by a continuous
i.v. infusion for the duration of the PET scan. Five of the tested drugs increased
total distribution volume of [11C]erlotinib in the brain (VT,brain) compared to
vehicle-treated animals (tariquidar, + 69%; erlotinib, + 19% and +23% for the
21.5 mg/kg and the 43 mg/kg dose, respectively; imatinib, + 22%; lapatinib, +
25%; and cyclosporine A, + 49%). For all drugs, increases in [11C]erlotinib brain
distribution were lower than in Abcb1a/b(−/−)Abcg2(−/−) mice (+149%), which suggested
that only partial ABCB1/ABCG2 inhibition was reached at the mouse BBB. The plasma
concentrations of the tested drugs at the time of the PET scan were higher than
clinically achievable plasma concentrations. Some of the tested drugs led to significant
increases in blood radioactivity concentrations measured at the end of the PET
scan (erlotinib, + 103% and +113% for the 21.5 mg/kg and the 43 mg/kg dose, respectively;
imatinib, + 125%; and cyclosporine A, + 101%), which was most likely caused by
decreased hepatobiliary excretion of radioactivity. Taken together, our data suggest
that some marketed tyrosine kinase inhibitors may be repurposed to inhibit ABCB1
and ABCG2 at the BBB. From a clinical perspective, moderate increases in brain
delivery despite the administration of high i.v. doses as well as peripheral drug–drug
interactions due to transporter inhibition in clearance organs question the translatability
of this concept.
article_processing_charge: No
author:
- first_name: Alexander
full_name: Traxl, Alexander
last_name: Traxl
- first_name: Severin
full_name: Mairinger, Severin
last_name: Mairinger
- first_name: Thomas
full_name: Filip, Thomas
last_name: Filip
- first_name: Michael
full_name: Sauberer, Michael
last_name: Sauberer
- first_name: Johann
full_name: Stanek, Johann
last_name: Stanek
- first_name: Stefan
full_name: Poschner, Stefan
last_name: Poschner
- first_name: Walter
full_name: Jäger, Walter
last_name: Jäger
- first_name: Viktoria
full_name: Zoufal, Viktoria
last_name: Zoufal
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Nicolas
full_name: Tournier, Nicolas
last_name: Tournier
- first_name: Martin
full_name: Bauer, Martin
last_name: Bauer
- first_name: Thomas
full_name: Wanek, Thomas
last_name: Wanek
- first_name: Oliver
full_name: Langer, Oliver
last_name: Langer
citation:
ama: Traxl A, Mairinger S, Filip T, et al. Inhibition of ABCB1 and ABCG2 at the
mouse blood-brain barrier with marketed drugs to improve brain delivery of the
model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics. 2019;16(3):1282-1293.
doi:10.1021/acs.molpharmaceut.8b01217
apa: Traxl, A., Mairinger, S., Filip, T., Sauberer, M., Stanek, J., Poschner, S.,
… Langer, O. (2019). Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier
with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate
[11C]erlotinib. Molecular Pharmaceutics. American Chemical Society. https://doi.org/10.1021/acs.molpharmaceut.8b01217
chicago: Traxl, Alexander, Severin Mairinger, Thomas Filip, Michael Sauberer, Johann
Stanek, Stefan Poschner, Walter Jäger, et al. “Inhibition of ABCB1 and ABCG2 at
the Mouse Blood-Brain Barrier with Marketed Drugs to Improve Brain Delivery of
the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Molecular Pharmaceutics.
American Chemical Society, 2019. https://doi.org/10.1021/acs.molpharmaceut.8b01217.
ieee: A. Traxl et al., “Inhibition of ABCB1 and ABCG2 at the mouse blood-brain
barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2
substrate [11C]erlotinib,” Molecular Pharmaceutics, vol. 16, no. 3. American
Chemical Society, pp. 1282–1293, 2019.
ista: Traxl A, Mairinger S, Filip T, Sauberer M, Stanek J, Poschner S, Jäger W,
Zoufal V, Novarino G, Tournier N, Bauer M, Wanek T, Langer O. 2019. Inhibition
of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve
brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics.
16(3), 1282–1293.
mla: Traxl, Alexander, et al. “Inhibition of ABCB1 and ABCG2 at the Mouse Blood-Brain
Barrier with Marketed Drugs to Improve Brain Delivery of the Model ABCB1/ABCG2
Substrate [11C]Erlotinib.” Molecular Pharmaceutics, vol. 16, no. 3, American
Chemical Society, 2019, pp. 1282–93, doi:10.1021/acs.molpharmaceut.8b01217.
short: A. Traxl, S. Mairinger, T. Filip, M. Sauberer, J. Stanek, S. Poschner, W.
Jäger, V. Zoufal, G. Novarino, N. Tournier, M. Bauer, T. Wanek, O. Langer, Molecular
Pharmaceutics 16 (2019) 1282–1293.
date_created: 2019-03-10T22:59:19Z
date_published: 2019-03-04T00:00:00Z
date_updated: 2023-08-25T08:02:51Z
day: '04'
department:
- _id: GaNo
doi: 10.1021/acs.molpharmaceut.8b01217
external_id:
isi:
- '000460600400031'
pmid:
- '30694684'
intvolume: ' 16'
isi: 1
issue: '3'
language:
- iso: eng
month: '03'
oa_version: None
page: 1282-1293
pmid: 1
publication: Molecular Pharmaceutics
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed
drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 16
year: '2019'
...
---
_id: '6470'
abstract:
- lang: eng
text: 'Investigating neuronal activity using genetically encoded Ca2+ indicators
in behaving animals is hampered by inaccuracies in spike inference from fluorescent
tracers. Here we combine two‐photon [Ca2+] imaging with cell‐attached recordings,
followed by post hoc determination of the expression level of GCaMP6f, to explore
how it affects the amplitude, kinetics and temporal summation of somatic [Ca2+]
transients in mouse hippocampal pyramidal cells (PCs). The amplitude of unitary
[Ca2+] transients (evoked by a single action potential) negatively correlates
with GCaMP6f expression, but displays large variability even among PCs with similarly
low expression levels. The summation of fluorescence signals is frequency‐dependent,
supralinear and also shows remarkable cell‐to‐cell variability. We performed experimental
data‐based simulations and found that spike inference error rates using MLspike
depend strongly on unitary peak amplitudes and GCaMP6f expression levels. We provide
simple methods for estimating the unitary [Ca2+] transients in individual weakly
GCaMP6f‐expressing PCs, with which we achieve spike inference error rates of ∼5%. '
article_processing_charge: No
article_type: original
author:
- first_name: Tímea
full_name: Éltes, Tímea
last_name: Éltes
- first_name: Miklos
full_name: Szoboszlay, Miklos
last_name: Szoboszlay
- first_name: Margit Katalin
full_name: Szigeti, Margit Katalin
id: 44F4BDC0-F248-11E8-B48F-1D18A9856A87
last_name: Szigeti
orcid: 0000-0001-9500-8758
- first_name: Zoltan
full_name: Nusser, Zoltan
last_name: Nusser
citation:
ama: Éltes T, Szoboszlay M, Szigeti MK, Nusser Z. Improved spike inference accuracy
by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing
hippocampal pyramidal cells. Journal of Physiology. 2019;597(11):2925–2947.
doi:10.1113/JP277681
apa: Éltes, T., Szoboszlay, M., Szigeti, M. K., & Nusser, Z. (2019). Improved
spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients
in weakly GCaMP6f-expressing hippocampal pyramidal cells. Journal of Physiology.
Wiley. https://doi.org/10.1113/JP277681
chicago: Éltes, Tímea, Miklos Szoboszlay, Margit Katalin Szigeti, and Zoltan Nusser.
“Improved Spike Inference Accuracy by Estimating the Peak Amplitude of Unitary
[Ca2+] Transients in Weakly GCaMP6f-Expressing Hippocampal Pyramidal Cells.” Journal
of Physiology. Wiley, 2019. https://doi.org/10.1113/JP277681.
ieee: T. Éltes, M. Szoboszlay, M. K. Szigeti, and Z. Nusser, “Improved spike inference
accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly
GCaMP6f-expressing hippocampal pyramidal cells,” Journal of Physiology,
vol. 597, no. 11. Wiley, pp. 2925–2947, 2019.
ista: Éltes T, Szoboszlay M, Szigeti MK, Nusser Z. 2019. Improved spike inference
accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly
GCaMP6f-expressing hippocampal pyramidal cells. Journal of Physiology. 597(11),
2925–2947.
mla: Éltes, Tímea, et al. “Improved Spike Inference Accuracy by Estimating the Peak
Amplitude of Unitary [Ca2+] Transients in Weakly GCaMP6f-Expressing Hippocampal
Pyramidal Cells.” Journal of Physiology, vol. 597, no. 11, Wiley, 2019,
pp. 2925–2947, doi:10.1113/JP277681.
short: T. Éltes, M. Szoboszlay, M.K. Szigeti, Z. Nusser, Journal of Physiology 597
(2019) 2925–2947.
date_created: 2019-05-19T21:59:17Z
date_published: 2019-06-01T00:00:00Z
date_updated: 2023-08-25T10:34:15Z
day: '01'
department:
- _id: GaNo
doi: 10.1113/JP277681
external_id:
isi:
- '000470780400013'
pmid:
- '31006863'
intvolume: ' 597'
isi: 1
issue: '11'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1113/JP277681
month: '06'
oa: 1
oa_version: Published Version
page: 2925–2947
pmid: 1
publication: Journal of Physiology
publication_identifier:
eissn:
- '14697793'
issn:
- '00223751'
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Improved spike inference accuracy by estimating the peak amplitude of unitary
[Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 597
year: '2019'
...
---
_id: '105'
abstract:
- lang: eng
text: 'Clinical Utility Gene Card. 1. Name of Disease (Synonyms): Pontocerebellar
hypoplasia type 9 (PCH9) and spastic paraplegia-63 (SPG63). 2. OMIM# of the Disease:
615809 and 615686. 3. Name of the Analysed Genes or DNA/Chromosome Segments: AMPD2
at 1p13.3. 4. OMIM# of the Gene(s): 102771.'
acknowledgement: 'This work was supported by EuroGentest2 (Unit 2: “Genetic testing
as part of health care”), a Coordination Action under FP7 (Grant Agreement Number
261469) and the European Society of Human Genetics. We acknowledge the participation
of the patients and their families in these studies, as well as the generous financial
support of the Lefroy and Handbury families. APLM was supported by an Australian
Postgraduate Award. PJL is supported by an NHMRC Career Development Fellowship (GNT1032364).
RJL is supported by a Melbourne Children’s Clinician Scientist Fellowship.'
article_processing_charge: No
article_type: original
author:
- first_name: Ashley
full_name: Marsh, Ashley
last_name: Marsh
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Paul
full_name: Lockhart, Paul
last_name: Lockhart
- first_name: Richard
full_name: Leventer, Richard
last_name: Leventer
citation:
ama: Marsh A, Novarino G, Lockhart P, Leventer R. CUGC for pontocerebellar hypoplasia
type 9 and spastic paraplegia-63. European Journal of Human Genetics. 2019;27:161-166.
doi:10.1038/s41431-018-0231-2
apa: Marsh, A., Novarino, G., Lockhart, P., & Leventer, R. (2019). CUGC for
pontocerebellar hypoplasia type 9 and spastic paraplegia-63. European Journal
of Human Genetics. Springer Nature. https://doi.org/10.1038/s41431-018-0231-2
chicago: Marsh, Ashley, Gaia Novarino, Paul Lockhart, and Richard Leventer. “CUGC
for Pontocerebellar Hypoplasia Type 9 and Spastic Paraplegia-63.” European
Journal of Human Genetics. Springer Nature, 2019. https://doi.org/10.1038/s41431-018-0231-2.
ieee: A. Marsh, G. Novarino, P. Lockhart, and R. Leventer, “CUGC for pontocerebellar
hypoplasia type 9 and spastic paraplegia-63,” European Journal of Human Genetics,
vol. 27. Springer Nature, pp. 161–166, 2019.
ista: Marsh A, Novarino G, Lockhart P, Leventer R. 2019. CUGC for pontocerebellar
hypoplasia type 9 and spastic paraplegia-63. European Journal of Human Genetics.
27, 161–166.
mla: Marsh, Ashley, et al. “CUGC for Pontocerebellar Hypoplasia Type 9 and Spastic
Paraplegia-63.” European Journal of Human Genetics, vol. 27, Springer Nature,
2019, pp. 161–66, doi:10.1038/s41431-018-0231-2.
short: A. Marsh, G. Novarino, P. Lockhart, R. Leventer, European Journal of Human
Genetics 27 (2019) 161–166.
date_created: 2018-12-11T11:44:39Z
date_published: 2019-01-01T00:00:00Z
date_updated: 2023-08-24T14:28:24Z
day: '01'
department:
- _id: GaNo
doi: 10.1038/s41431-018-0231-2
external_id:
isi:
- '000454111500019'
pmid:
- '30089829'
intvolume: ' 27'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41431-018-0231-2
month: '01'
oa: 1
oa_version: Published Version
page: 161-166
pmid: 1
publication: European Journal of Human Genetics
publication_status: published
publisher: Springer Nature
publist_id: '7949'
quality_controlled: '1'
scopus_import: '1'
status: public
title: CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 27
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: '691'
abstract:
- lang: eng
text: "Background: Transport protein particle (TRAPP) is a multisubunit complex
that regulates membrane trafficking through the Golgi apparatus. The clinical
phenotype associated with mutations in various TRAPP subunits has allowed elucidation
of their functions in specific tissues. The role of some subunits in human disease,
however, has not been fully established, and their functions remain uncertain.\r\n\r\nObjective:
We aimed to expand the range of neurodevelopmental disorders associated with mutations
in TRAPP subunits by exome sequencing of consanguineous families.\r\n\r\nMethods:
Linkage and homozygosity mapping and candidate gene analysis were used to identify
homozygous mutations in families. Patient fibroblasts were used to study splicing
defect and zebrafish to model the disease.\r\n\r\nResults: We identified six individuals
from three unrelated families with a founder homozygous splice mutation in TRAPPC6B,
encoding a core subunit of the complex TRAPP I. Patients manifested a neurodevelopmental
disorder characterised by microcephaly, epilepsy and autistic features, and showed
splicing defect. Zebrafish trappc6b morphants replicated the human phenotype,
displaying decreased head size and neuronal hyperexcitability, leading to a lower
seizure threshold.\r\n\r\nConclusion: This study provides clinical and functional
evidence of the role of TRAPPC6B in brain development and function."
article_processing_charge: No
article_type: original
author:
- first_name: Isaac
full_name: Marin Valencia, Isaac
last_name: Marin Valencia
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Anide
full_name: Johansen, Anide
last_name: Johansen
- first_name: Başak
full_name: Rosti, Başak
last_name: Rosti
- first_name: Mahmoud
full_name: Issa, Mahmoud
last_name: Issa
- first_name: Damir
full_name: Musaev, Damir
last_name: Musaev
- first_name: Gifty
full_name: Bhat, Gifty
last_name: Bhat
- first_name: Eric
full_name: Scott, Eric
last_name: Scott
- first_name: Jennifer
full_name: Silhavy, Jennifer
last_name: Silhavy
- first_name: Valentina
full_name: Stanley, Valentina
last_name: Stanley
- first_name: Rasim
full_name: Rosti, Rasim
last_name: Rosti
- first_name: Jeremy
full_name: Gleeson, Jeremy
last_name: Gleeson
- first_name: Farhad
full_name: Imam, Farhad
last_name: Imam
- first_name: Maha
full_name: Zaki, Maha
last_name: Zaki
- first_name: Joseph
full_name: Gleeson, Joseph
last_name: Gleeson
citation:
ama: Marin Valencia I, Novarino G, Johansen A, et al. A homozygous founder mutation
in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly
epilepsy and autistic features. Journal of Medical Genetics. 2018;55(1):48-54.
doi:10.1136/jmedgenet-2017-104627
apa: Marin Valencia, I., Novarino, G., Johansen, A., Rosti, B., Issa, M., Musaev,
D., … Gleeson, J. (2018). A homozygous founder mutation in TRAPPC6B associates
with a neurodevelopmental disorder characterised by microcephaly epilepsy and
autistic features. Journal of Medical Genetics. BMJ Publishing Group. https://doi.org/10.1136/jmedgenet-2017-104627
chicago: Marin Valencia, Isaac, Gaia Novarino, Anide Johansen, Başak Rosti, Mahmoud
Issa, Damir Musaev, Gifty Bhat, et al. “A Homozygous Founder Mutation in TRAPPC6B
Associates with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy
and Autistic Features.” Journal of Medical Genetics. BMJ Publishing Group,
2018. https://doi.org/10.1136/jmedgenet-2017-104627.
ieee: I. Marin Valencia et al., “A homozygous founder mutation in TRAPPC6B
associates with a neurodevelopmental disorder characterised by microcephaly epilepsy
and autistic features,” Journal of Medical Genetics, vol. 55, no. 1. BMJ
Publishing Group, pp. 48–54, 2018.
ista: Marin Valencia I, Novarino G, Johansen A, Rosti B, Issa M, Musaev D, Bhat
G, Scott E, Silhavy J, Stanley V, Rosti R, Gleeson J, Imam F, Zaki M, Gleeson
J. 2018. A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental
disorder characterised by microcephaly epilepsy and autistic features. Journal
of Medical Genetics. 55(1), 48–54.
mla: Marin Valencia, Isaac, et al. “A Homozygous Founder Mutation in TRAPPC6B Associates
with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy and
Autistic Features.” Journal of Medical Genetics, vol. 55, no. 1, BMJ Publishing
Group, 2018, pp. 48–54, doi:10.1136/jmedgenet-2017-104627.
short: I. Marin Valencia, G. Novarino, A. Johansen, B. Rosti, M. Issa, D. Musaev,
G. Bhat, E. Scott, J. Silhavy, V. Stanley, R. Rosti, J. Gleeson, F. Imam, M. Zaki,
J. Gleeson, Journal of Medical Genetics 55 (2018) 48–54.
date_created: 2018-12-11T11:47:57Z
date_published: 2018-01-01T00:00:00Z
date_updated: 2023-10-16T09:55:43Z
day: '01'
department:
- _id: GaNo
doi: 10.1136/jmedgenet-2017-104627
external_id:
isi:
- '000418199800007'
pmid:
- '28626029'
intvolume: ' 55'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056005/
month: '01'
oa: 1
oa_version: Submitted Version
page: 48 - 54
pmid: 1
project:
- _id: 254BA948-B435-11E9-9278-68D0E5697425
grant_number: '401299'
name: Probing development and reversibility of autism spectrum disorders
publication: Journal of Medical Genetics
publication_identifier:
issn:
- 0022-2593
publication_status: published
publisher: BMJ Publishing Group
publist_id: '7016'
quality_controlled: '1'
scopus_import: '1'
status: public
title: A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental
disorder characterised by microcephaly epilepsy and autistic features
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 55
year: '2018'
...
---
_id: '456'
abstract:
- lang: eng
text: 'Inhibition of the endoplasmic reticulum stress pathway may hold the key to
Zika virus-associated microcephaly treatment. '
article_number: eaar7514
author:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: 'Novarino G. Zika-associated microcephaly: Reduce the stress and race for the
treatment. Science Translational Medicine. 2018;10(423). doi:10.1126/scitranslmed.aar7514'
apa: 'Novarino, G. (2018). Zika-associated microcephaly: Reduce the stress and race
for the treatment. Science Translational Medicine. American Association
for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aar7514'
chicago: 'Novarino, Gaia. “Zika-Associated Microcephaly: Reduce the Stress and Race
for the Treatment.” Science Translational Medicine. American Association
for the Advancement of Science, 2018. https://doi.org/10.1126/scitranslmed.aar7514.'
ieee: 'G. Novarino, “Zika-associated microcephaly: Reduce the stress and race for
the treatment,” Science Translational Medicine, vol. 10, no. 423. American
Association for the Advancement of Science, 2018.'
ista: 'Novarino G. 2018. Zika-associated microcephaly: Reduce the stress and race
for the treatment. Science Translational Medicine. 10(423), eaar7514.'
mla: 'Novarino, Gaia. “Zika-Associated Microcephaly: Reduce the Stress and Race
for the Treatment.” Science Translational Medicine, vol. 10, no. 423, eaar7514,
American Association for the Advancement of Science, 2018, doi:10.1126/scitranslmed.aar7514.'
short: G. Novarino, Science Translational Medicine 10 (2018).
date_created: 2018-12-11T11:46:34Z
date_published: 2018-01-10T00:00:00Z
date_updated: 2021-01-12T07:59:42Z
day: '10'
department:
- _id: GaNo
doi: 10.1126/scitranslmed.aar7514
intvolume: ' 10'
issue: '423'
language:
- iso: eng
month: '01'
oa_version: None
publication: Science Translational Medicine
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '7365'
quality_controlled: '1'
scopus_import: 1
status: public
title: 'Zika-associated microcephaly: Reduce the stress and race for the treatment'
type: journal_article
user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 10
year: '2018'
...