---
_id: '11460'
abstract:
- lang: eng
  text: "Background: Proper cerebral cortical development depends on the tightly orchestrated
    migration of newly born neurons from the inner ventricular and subventricular
    zones to the outer cortical plate. Any disturbance in this process during prenatal
    stages may lead to neuronal migration disorders (NMDs), which can vary in extent
    from focal to global. Furthermore, NMDs show a substantial comorbidity with other
    neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous
    work demonstrated focal neuronal migration defects in mice carrying loss-of-function
    alleles of the recognized autism risk gene WDFY3. However, the cellular origins
    of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide
    critical insight into WDFY3-dependent disease pathology.\r\nMethods: Here, in
    an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic
    analysis with double markers (MADM). MADM technology enabled us to genetically
    distinctly track and phenotypically analyze mutant and wild-type cells concomitantly
    in vivo using immunofluorescent techniques.\r\nResults: We revealed a cell autonomous
    requirement of WDFY3 for accurate laminar positioning of cortical projection neurons
    and elimination of mispositioned cells during early postnatal life. In addition,
    we identified significant deviations in dendritic arborization, as well as synaptic
    density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant
    neurons in Wdfy3-MADM reporter mice at postnatal stages.\r\nLimitations: While
    Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD
    pathology that remain inaccessible to investigation in humans, like most animal
    models, they do not a perfectly replicate all aspects of human ASD biology. The
    lack of human data makes it indeterminate whether morphological deviations described
    here apply to ASD patients or some of the other neurodevelopmental conditions
    associated with WDFY3 mutation.\r\nConclusions: Our genetic approach revealed
    several cell autonomous requirements of WDFY3 in neuronal development that could
    underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions.
    The results are also consistent with findings in other ASD animal models and patients
    and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity
    in postnatal life."
acknowledgement: "This study was funded by NIMH R21MH115347 to KSZ. KSZ is further
  supported by Shriners Hospitals for Children.\r\nWe would like to thank Angelo Harlan
  de Crescenzo for early contributions to this project."
article_number: '27'
article_processing_charge: No
article_type: original
author:
- first_name: Zachary A.
  full_name: Schaaf, Zachary A.
  last_name: Schaaf
- first_name: Lyvin
  full_name: Tat, Lyvin
  last_name: Tat
- first_name: Noemi
  full_name: Cannizzaro, Noemi
  last_name: Cannizzaro
- first_name: Ralph
  full_name: Green, Ralph
  last_name: Green
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
- first_name: Konstantinos S.
  full_name: Zarbalis, Konstantinos S.
  last_name: Zarbalis
citation:
  ama: Schaaf ZA, Tat L, Cannizzaro N, et al. WDFY3 mutation alters laminar position
    and morphology of cortical neurons. <i>Molecular Autism</i>. 2022;13. doi:<a href="https://doi.org/10.1186/s13229-022-00508-3">10.1186/s13229-022-00508-3</a>
  apa: Schaaf, Z. A., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer,
    S., &#38; Zarbalis, K. S. (2022). WDFY3 mutation alters laminar position and morphology
    of cortical neurons. <i>Molecular Autism</i>. Springer Nature. <a href="https://doi.org/10.1186/s13229-022-00508-3">https://doi.org/10.1186/s13229-022-00508-3</a>
  chicago: Schaaf, Zachary A., Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke,
    Simon Hippenmeyer, and Konstantinos S. Zarbalis. “WDFY3 Mutation Alters Laminar
    Position and Morphology of Cortical Neurons.” <i>Molecular Autism</i>. Springer
    Nature, 2022. <a href="https://doi.org/10.1186/s13229-022-00508-3">https://doi.org/10.1186/s13229-022-00508-3</a>.
  ieee: Z. A. Schaaf <i>et al.</i>, “WDFY3 mutation alters laminar position and morphology
    of cortical neurons,” <i>Molecular Autism</i>, vol. 13. Springer Nature, 2022.
  ista: Schaaf ZA, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis
    KS. 2022. WDFY3 mutation alters laminar position and morphology of cortical neurons.
    Molecular Autism. 13, 27.
  mla: Schaaf, Zachary A., et al. “WDFY3 Mutation Alters Laminar Position and Morphology
    of Cortical Neurons.” <i>Molecular Autism</i>, vol. 13, 27, Springer Nature, 2022,
    doi:<a href="https://doi.org/10.1186/s13229-022-00508-3">10.1186/s13229-022-00508-3</a>.
  short: Z.A. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer,
    K.S. Zarbalis, Molecular Autism 13 (2022).
date_created: 2022-06-23T14:28:55Z
date_published: 2022-06-22T00:00:00Z
date_updated: 2023-08-03T07:21:32Z
day: '22'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1186/s13229-022-00508-3
external_id:
  isi:
  - '000814641400001'
file:
- access_level: open_access
  checksum: 525d2618e855139089bbfc3e3d49d1b2
  content_type: application/pdf
  creator: dernst
  date_created: 2022-06-24T08:22:59Z
  date_updated: 2022-06-24T08:22:59Z
  file_id: '11461'
  file_name: 2022_MolecularAutism_Schaaf.pdf
  file_size: 7552298
  relation: main_file
  success: 1
file_date_updated: 2022-06-24T08:22:59Z
has_accepted_license: '1'
intvolume: '        13'
isi: 1
keyword:
- Psychiatry and Mental health
- Developmental Biology
- Developmental Neuroscience
- Molecular Biology
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
publication: Molecular Autism
publication_identifier:
  issn:
  - 2040-2392
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: erratum
    url: https://doi.org/10.1186/s13229-023-00539-4
status: public
title: WDFY3 mutation alters laminar position and morphology of cortical neurons
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: 13
year: '2022'
...