---
_id: '12115'
acknowledgement: This work was supported by European Commission’s Seventh Framework
  Programme under Grant Agreement No. 279113 (OCTIPS; www.octips.eu).
article_processing_charge: No
article_type: original
author:
- first_name: Jacek
  full_name: Glajzer, Jacek
  last_name: Glajzer
- first_name: Dan Cacsire
  full_name: Castillo-Tong, Dan Cacsire
  last_name: Castillo-Tong
- first_name: Rolf
  full_name: Richter, Rolf
  last_name: Richter
- first_name: Ignace
  full_name: Vergote, Ignace
  last_name: Vergote
- first_name: Hagen
  full_name: Kulbe, Hagen
  last_name: Kulbe
- first_name: Adriaan
  full_name: Vanderstichele, Adriaan
  last_name: Vanderstichele
- first_name: Ilary
  full_name: Ruscito, Ilary
  last_name: Ruscito
- first_name: Fabian
  full_name: Trillsch, Fabian
  last_name: Trillsch
- first_name: Alexander
  full_name: Mustea, Alexander
  last_name: Mustea
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Charlie
  full_name: Gourley, Charlie
  last_name: Gourley
- first_name: Hani
  full_name: Gabra, Hani
  last_name: Gabra
- first_name: Eliane T.
  full_name: Taube, Eliane T.
  last_name: Taube
- first_name: Oliver
  full_name: Dorigo, Oliver
  last_name: Dorigo
- first_name: David
  full_name: Horst, David
  last_name: Horst
- first_name: Carlotta
  full_name: Keunecke, Carlotta
  last_name: Keunecke
- first_name: Joanna
  full_name: Baum, Joanna
  last_name: Baum
- first_name: Timothy
  full_name: Angelotti, Timothy
  last_name: Angelotti
- first_name: Jalid
  full_name: Sehouli, Jalid
  last_name: Sehouli
- first_name: Elena Ioana
  full_name: Braicu, Elena Ioana
  last_name: Braicu
citation:
  ama: 'Glajzer J, Castillo-Tong DC, Richter R, et al. ASO Visual Abstract: Impact
    of BRCA mutation status on tumor dissemination pattern, surgical outcome, and
    patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC).
    A multicenter, retrospective study of the ovarian cancer therapy—innovative models
    prolong survival (OCTIPS) consortium. <i>Annals of Surgical Oncology</i>. 2023;30:46-47.
    doi:<a href="https://doi.org/10.1245/s10434-022-12681-z">10.1245/s10434-022-12681-z</a>'
  apa: 'Glajzer, J., Castillo-Tong, D. C., Richter, R., Vergote, I., Kulbe, H., Vanderstichele,
    A., … Braicu, E. I. (2023). ASO Visual Abstract: Impact of BRCA mutation status
    on tumor dissemination pattern, surgical outcome, and patient survival in primary
    and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective
    study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS)
    consortium. <i>Annals of Surgical Oncology</i>. Springer Nature. <a href="https://doi.org/10.1245/s10434-022-12681-z">https://doi.org/10.1245/s10434-022-12681-z</a>'
  chicago: 'Glajzer, Jacek, Dan Cacsire Castillo-Tong, Rolf Richter, Ignace Vergote,
    Hagen Kulbe, Adriaan Vanderstichele, Ilary Ruscito, et al. “ASO Visual Abstract:
    Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome,
    and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer
    (HGSOC). A Multicenter, Retrospective Study of the Ovarian Cancer Therapy—Innovative
    Models Prolong Survival (OCTIPS) Consortium.” <i>Annals of Surgical Oncology</i>.
    Springer Nature, 2023. <a href="https://doi.org/10.1245/s10434-022-12681-z">https://doi.org/10.1245/s10434-022-12681-z</a>.'
  ieee: 'J. Glajzer <i>et al.</i>, “ASO Visual Abstract: Impact of BRCA mutation status
    on tumor dissemination pattern, surgical outcome, and patient survival in primary
    and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective
    study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS)
    consortium,” <i>Annals of Surgical Oncology</i>, vol. 30. Springer Nature, pp.
    46–47, 2023.'
  ista: 'Glajzer J, Castillo-Tong DC, Richter R, Vergote I, Kulbe H, Vanderstichele
    A, Ruscito I, Trillsch F, Mustea A, Kreuzinger C, Gourley C, Gabra H, Taube ET,
    Dorigo O, Horst D, Keunecke C, Baum J, Angelotti T, Sehouli J, Braicu EI. 2023.
    ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern,
    surgical outcome, and patient survival in primary and recurrent high-grade serous
    ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer
    therapy—innovative models prolong survival (OCTIPS) consortium. Annals of Surgical
    Oncology. 30, 46–47.'
  mla: 'Glajzer, Jacek, et al. “ASO Visual Abstract: Impact of BRCA Mutation Status
    on Tumor Dissemination Pattern, Surgical Outcome, and Patient Survival in Primary
    and Recurrent High-Grade Serous Ovarian Cancer (HGSOC). A Multicenter, Retrospective
    Study of the Ovarian Cancer Therapy—Innovative Models Prolong Survival (OCTIPS)
    Consortium.” <i>Annals of Surgical Oncology</i>, vol. 30, Springer Nature, 2023,
    pp. 46–47, doi:<a href="https://doi.org/10.1245/s10434-022-12681-z">10.1245/s10434-022-12681-z</a>.'
  short: J. Glajzer, D.C. Castillo-Tong, R. Richter, I. Vergote, H. Kulbe, A. Vanderstichele,
    I. Ruscito, F. Trillsch, A. Mustea, C. Kreuzinger, C. Gourley, H. Gabra, E.T.
    Taube, O. Dorigo, D. Horst, C. Keunecke, J. Baum, T. Angelotti, J. Sehouli, E.I.
    Braicu, Annals of Surgical Oncology 30 (2023) 46–47.
date_created: 2023-01-12T11:56:22Z
date_published: 2023-01-01T00:00:00Z
date_updated: 2023-09-05T15:18:36Z
day: '01'
department:
- _id: JoDa
doi: 10.1245/s10434-022-12681-z
external_id:
  isi:
  - '000879151800001'
intvolume: '        30'
isi: 1
keyword:
- Oncology
- Surgery
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1245/s10434-022-12681-z
month: '01'
oa: 1
oa_version: Published Version
page: 46-47
publication: Annals of Surgical Oncology
publication_identifier:
  eissn:
  - 1534-4681
  issn:
  - 1068-9265
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
  - id: '12205'
    relation: other
    status: public
scopus_import: '1'
status: public
title: 'ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination
  pattern, surgical outcome, and patient survival in primary and recurrent high-grade
  serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian
  cancer therapy—innovative models prolong survival (OCTIPS) consortium'
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 30
year: '2023'
...
---
_id: '12205'
abstract:
- lang: eng
  text: "Background: This study seeks to evaluate the impact of breast cancer (BRCA)
    gene status on tumor dissemination pattern, surgical outcome and survival in a
    multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian
    cancer (rOC).\r\n\r\nPatients and Methods: Medical records and follow-up data
    from 190 patients were gathered retrospectively. All patients had surgery at pOC
    and at least one further rOC surgery at four European high-volume centers. Patients
    were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut)
    and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor
    presentation, surgical outcome and survival data were analyzed between the two
    groups.\r\n\r\nResults: Patients with BRCAmut disease were on average 4 years
    younger and had significantly more tumor involvement upon diagnosis. Patients
    with BRCAmut disease showed higher debulking rates at all stages. Multivariate
    analysis showed that only patient age had significant predictive value for complete
    tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated
    with optimal debulking. Patients with BRCAmut disease showed significantly prolonged
    overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged
    in the BRCAmut group at all stages as well, reaching statistical significance
    during recurrence.\r\n\r\nConclusions: Patients with BRCAmut disease showed a
    more aggressive course of disease with earlier onset and more extensive tumor
    dissemination at pOC. However, surgical outcome and OS were significantly better
    in patients with BRCAmut disease compared with patients with BRCAwt disease. We
    therefore propose to consider BRCAmut status in regard to patient selection for
    cytoreductive surgery, especially in rOC."
acknowledgement: "E.I.B. is a Feodor Lynen fellow of the Humboldt Foundation and a
  participant of the Charité Clinical Scientist Program funded by the Charité Universitätsmedizin
  Berlin and the Berlin Institute of Health. This work was supported by European Commission’s
  Seventh Framework Programme under grant agreement no. 279113 (OCTIPS; www.octips.eu).\r\nOpen
  Access funding enabled and organized by Projekt DEAL."
article_processing_charge: No
article_type: original
author:
- first_name: Jacek
  full_name: Glajzer, Jacek
  last_name: Glajzer
- first_name: Dan Cacsire
  full_name: Castillo-Tong, Dan Cacsire
  last_name: Castillo-Tong
- first_name: Rolf
  full_name: Richter, Rolf
  last_name: Richter
- first_name: Ignace
  full_name: Vergote, Ignace
  last_name: Vergote
- first_name: Hagen
  full_name: Kulbe, Hagen
  last_name: Kulbe
- first_name: Adriaan
  full_name: Vanderstichele, Adriaan
  last_name: Vanderstichele
- first_name: Ilary
  full_name: Ruscito, Ilary
  last_name: Ruscito
- first_name: Fabian
  full_name: Trillsch, Fabian
  last_name: Trillsch
- first_name: Alexander
  full_name: Mustea, Alexander
  last_name: Mustea
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Charlie
  full_name: Gourley, Charlie
  last_name: Gourley
- first_name: Hani
  full_name: Gabra, Hani
  last_name: Gabra
- first_name: Eliane T.
  full_name: Taube, Eliane T.
  last_name: Taube
- first_name: Oliver
  full_name: Dorigo, Oliver
  last_name: Dorigo
- first_name: David
  full_name: Horst, David
  last_name: Horst
- first_name: Carlotta
  full_name: Keunecke, Carlotta
  last_name: Keunecke
- first_name: Joanna
  full_name: Baum, Joanna
  last_name: Baum
- first_name: Timothy
  full_name: Angelotti, Timothy
  last_name: Angelotti
- first_name: Jalid
  full_name: Sehouli, Jalid
  last_name: Sehouli
- first_name: Elena Ioana
  full_name: Braicu, Elena Ioana
  last_name: Braicu
citation:
  ama: 'Glajzer J, Castillo-Tong DC, Richter R, et al. Impact of BRCA mutation status
    on tumor dissemination pattern, surgical outcome and patient survival in primary
    and recurrent high-grade serous ovarian cancer: A multicenter retrospective study
    by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium.
    <i>Annals of Surgical Oncology</i>. 2023;30:35-45. doi:<a href="https://doi.org/10.1245/s10434-022-12459-3">10.1245/s10434-022-12459-3</a>'
  apa: 'Glajzer, J., Castillo-Tong, D. C., Richter, R., Vergote, I., Kulbe, H., Vanderstichele,
    A., … Braicu, E. I. (2023). Impact of BRCA mutation status on tumor dissemination
    pattern, surgical outcome and patient survival in primary and recurrent high-grade
    serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer
    Therapy-Innovative Models Prolong Survival (OCTIPS) consortium. <i>Annals of Surgical
    Oncology</i>. Springer Nature. <a href="https://doi.org/10.1245/s10434-022-12459-3">https://doi.org/10.1245/s10434-022-12459-3</a>'
  chicago: 'Glajzer, Jacek, Dan Cacsire Castillo-Tong, Rolf Richter, Ignace Vergote,
    Hagen Kulbe, Adriaan Vanderstichele, Ilary Ruscito, et al. “Impact of BRCA Mutation
    Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in
    Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective
    Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.”
    <i>Annals of Surgical Oncology</i>. Springer Nature, 2023. <a href="https://doi.org/10.1245/s10434-022-12459-3">https://doi.org/10.1245/s10434-022-12459-3</a>.'
  ieee: 'J. Glajzer <i>et al.</i>, “Impact of BRCA mutation status on tumor dissemination
    pattern, surgical outcome and patient survival in primary and recurrent high-grade
    serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer
    Therapy-Innovative Models Prolong Survival (OCTIPS) consortium,” <i>Annals of
    Surgical Oncology</i>, vol. 30. Springer Nature, pp. 35–45, 2023.'
  ista: 'Glajzer J, Castillo-Tong DC, Richter R, Vergote I, Kulbe H, Vanderstichele
    A, Ruscito I, Trillsch F, Mustea A, Kreuzinger C, Gourley C, Gabra H, Taube ET,
    Dorigo O, Horst D, Keunecke C, Baum J, Angelotti T, Sehouli J, Braicu EI. 2023.
    Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome
    and patient survival in primary and recurrent high-grade serous ovarian cancer:
    A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models
    Prolong Survival (OCTIPS) consortium. Annals of Surgical Oncology. 30, 35–45.'
  mla: 'Glajzer, Jacek, et al. “Impact of BRCA Mutation Status on Tumor Dissemination
    Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade
    Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer
    Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.” <i>Annals of
    Surgical Oncology</i>, vol. 30, Springer Nature, 2023, pp. 35–45, doi:<a href="https://doi.org/10.1245/s10434-022-12459-3">10.1245/s10434-022-12459-3</a>.'
  short: J. Glajzer, D.C. Castillo-Tong, R. Richter, I. Vergote, H. Kulbe, A. Vanderstichele,
    I. Ruscito, F. Trillsch, A. Mustea, C. Kreuzinger, C. Gourley, H. Gabra, E.T.
    Taube, O. Dorigo, D. Horst, C. Keunecke, J. Baum, T. Angelotti, J. Sehouli, E.I.
    Braicu, Annals of Surgical Oncology 30 (2023) 35–45.
date_created: 2023-01-16T09:44:36Z
date_published: 2023-01-01T00:00:00Z
date_updated: 2023-09-05T15:18:37Z
day: '01'
ddc:
- '610'
department:
- _id: JoDa
doi: 10.1245/s10434-022-12459-3
external_id:
  isi:
  - '000852125500006'
file:
- access_level: open_access
  checksum: 36a1200e1011f4b2155a8041d0308f34
  content_type: application/pdf
  creator: dernst
  date_created: 2023-02-02T13:01:20Z
  date_updated: 2023-02-02T13:01:20Z
  file_id: '12490'
  file_name: 2023_AnnalsSurgicalOncology_Glajzer.pdf
  file_size: 365865
  relation: main_file
  success: 1
file_date_updated: 2023-02-02T13:01:20Z
has_accepted_license: '1'
intvolume: '        30'
isi: 1
keyword:
- Oncology
- Surgery
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 35-45
publication: Annals of Surgical Oncology
publication_identifier:
  eissn:
  - 1534-4681
  issn:
  - 1068-9265
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
  - id: '12115'
    relation: other
    status: public
scopus_import: '1'
status: public
title: 'Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome
  and patient survival in primary and recurrent high-grade serous ovarian cancer:
  A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models
  Prolong Survival (OCTIPS) consortium'
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 30
year: '2023'
...
---
_id: '9429'
abstract:
- lang: eng
  text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
    lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency
    leads to motor coordination deficits as well as ASD-relevant social and cognitive
    impairments. However, induction of Cul3 haploinsufficiency later in life does
    not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during
    a critical developmental window. Here we show that Cul3 is essential to regulate
    neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice
    display cortical lamination abnormalities. At the molecular level, we found that
    Cul3 controls neuronal migration by tightly regulating the amount of Plastin3
    (Pls3), a previously unrecognized player of neural migration. Furthermore, we
    found that Pls3 cell-autonomously regulates cell migration by regulating actin
    cytoskeleton organization, and its levels are inversely proportional to neural
    migration speed. Finally, we provide evidence that cellular phenotypes associated
    with autism-linked gene haploinsufficiency can be rescued by transcriptional activation
    of the intact allele in vitro, offering a proof of concept for a potential therapeutic
    approach for ASDs.
acknowledged_ssus:
- _id: PreCl
acknowledgement: We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A.
  Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the
  management of our animal colony, as well as M. Schunn and the Preclinical Facility
  team for technical assistance. We thank K. Heesom and her team at the University
  of Bristol Proteomics Facility for the proteomics sample preparation, data generation,
  and analysis support. We thank Y. B. Simon for kindly providing the plasmid for
  lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration
  and the fruitful discussions. This work was supported by the ISTPlus postdoctoral
  fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon
  2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by
  the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D
  (I3600-B27).
article_number: '3058'
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: 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: Georgi A
  full_name: Dimchev, Georgi A
  id: 38C393BE-F248-11E8-B48F-1D18A9856A87
  last_name: Dimchev
  orcid: 0000-0001-8370-6161
- 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: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- 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: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
- 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.
    <i>Nature Communications</i>. 2021;12(1). doi:<a href="https://doi.org/10.1038/s41467-021-23123-x">10.1038/s41467-021-23123-x</a>
  apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A.,
    Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis
    and cell migration during a critical window of brain development. <i>Nature Communications</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41467-021-23123-x">https://doi.org/10.1038/s41467-021-23123-x</a>
  chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
    Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton
    Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.”
    <i>Nature Communications</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s41467-021-23123-x">https://doi.org/10.1038/s41467-021-23123-x</a>.
  ieee: J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis
    and cell migration during a critical window of brain development,” <i>Nature Communications</i>,
    vol. 12, no. 1. Springer Nature, 2021.
  ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer
    CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino
    G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during
    a critical window of brain development. Nature Communications. 12(1), 3058.
  mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
    and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>,
    vol. 12, no. 1, 3058, Springer Nature, 2021, doi:<a href="https://doi.org/10.1038/s41467-021-23123-x">10.1038/s41467-021-23123-x</a>.
  short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas,
    C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur,
    J.G. Danzl, G. Novarino, Nature Communications 12 (2021).
date_created: 2021-05-28T11:49:46Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2024-09-10T12:04:26Z
day: '24'
ddc:
- '572'
department:
- _id: GaNo
- _id: JoDa
- _id: FlSc
- _id: MiSi
- _id: LifeSc
- _id: Bio
doi: 10.1038/s41467-021-23123-x
ec_funded: 1
external_id:
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  - '000658769900010'
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file_date_updated: 2021-05-28T12:39:43Z
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intvolume: '        12'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _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
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
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  grant_number: F07807
  name: Neural stem cells in autism and epilepsy
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  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: press_release
    url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/
  record:
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    status: public
  - id: '12401'
    relation: dissertation_contains
    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.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: 12
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.
    <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2020.01.10.902064 ">10.1101/2020.01.10.902064
    </a>
  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. <i>bioRxiv</i>.
    Cold Spring Harbor Laboratory. <a href="https://doi.org/10.1101/2020.01.10.902064
    ">https://doi.org/10.1101/2020.01.10.902064 </a>
  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.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href="https://doi.org/10.1101/2020.01.10.902064
    ">https://doi.org/10.1101/2020.01.10.902064 </a>.
  ieee: J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis
    and cell migration during a critical window of brain development,” <i>bioRxiv</i>.
    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, <a href="https://doi.org/10.1101/2020.01.10.902064 ">10.1101/2020.01.10.902064
    </a>.
  mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
    and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>,
    Cold Spring Harbor Laboratory, doi:<a href="https://doi.org/10.1101/2020.01.10.902064
    ">10.1101/2020.01.10.902064 </a>.
  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 '
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  creator: rsix
  date_created: 2020-05-05T14:31:19Z
  date_updated: 2020-07-14T12:48:03Z
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  file_name: 2020.01.10.902064v1.full.pdf
  file_size: 2931370
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file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
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'
...