---
_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).
corr_author: '1'
date_created: 2021-05-28T11:49:46Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2026-08-17T22:30:10Z
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:
  isi:
  - '000658769900010'
file:
- access_level: open_access
  checksum: 337e0f7959c35ec959984cacdcb472ba
  content_type: application/pdf
  creator: kschuh
  date_created: 2021-05-28T12:39:43Z
  date_updated: 2021-05-28T12:39:43Z
  file_id: '9430'
  file_name: 2021_NatureCommunications_Morandell.pdf
  file_size: 9358599
  relation: main_file
  success: 1
file_date_updated: 2021-05-28T12:39:43Z
has_accepted_license: '1'
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
  name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
  grant_number: F7807
  name: Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem
    cells in autism and epilepsy
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  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/
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  - id: '19557'
    relation: dissertation_contains
    status: public
  - id: '7800'
    relation: earlier_version
    status: public
  - id: '12401'
    relation: dissertation_contains
    status: public
scopus_import: '1'
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'
...