---
_id: '10792'
abstract:
- lang: eng
  text: "Background\r\nProper 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\r\nHere,
    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\r\nWe 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. Limitations 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.\r\nConclusions\r\n\uFEFFOur genetic approach revealed several
    cell autonomous requirements of Wdfy3 in neuronal development that could underly
    the pathogenic mechanisms of WDFY3-related ASD 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."
article_processing_charge: No
author:
- first_name: Zachary
  full_name: Schaaf, Zachary
  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: K
  full_name: Zarbalis, K
  last_name: Zarbalis
citation:
  ama: Schaaf Z, Tat L, Cannizzaro N, et al. WDFY3 cell autonomously controls neuronal
    migration. doi:<a href="https://doi.org/10.21203/rs.3.rs-1316167/v1">10.21203/rs.3.rs-1316167/v1</a>
  apa: Schaaf, Z., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer, S.,
    &#38; Zarbalis, K. (n.d.). WDFY3 cell autonomously controls neuronal migration.
    Research Square. <a href="https://doi.org/10.21203/rs.3.rs-1316167/v1">https://doi.org/10.21203/rs.3.rs-1316167/v1</a>
  chicago: Schaaf, Zachary, Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke,
    Simon Hippenmeyer, and K Zarbalis. “WDFY3 Cell Autonomously Controls Neuronal
    Migration.” Research Square, n.d. <a href="https://doi.org/10.21203/rs.3.rs-1316167/v1">https://doi.org/10.21203/rs.3.rs-1316167/v1</a>.
  ieee: Z. Schaaf <i>et al.</i>, “WDFY3 cell autonomously controls neuronal migration.”
    Research Square.
  ista: Schaaf Z, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis
    K. WDFY3 cell autonomously controls neuronal migration. <a href="https://doi.org/10.21203/rs.3.rs-1316167/v1">10.21203/rs.3.rs-1316167/v1</a>.
  mla: Schaaf, Zachary, et al. <i>WDFY3 Cell Autonomously Controls Neuronal Migration</i>.
    Research Square, doi:<a href="https://doi.org/10.21203/rs.3.rs-1316167/v1">10.21203/rs.3.rs-1316167/v1</a>.
  short: Z. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer, K.
    Zarbalis, (n.d.).
date_created: 2022-02-25T07:53:26Z
date_published: 2022-02-16T00:00:00Z
date_updated: 2023-10-17T13:06:52Z
day: '16'
department:
- _id: SiHi
doi: 10.21203/rs.3.rs-1316167/v1
external_id:
  pmid:
  - PPR454733
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.21203/rs.3.rs-1316167/v1
month: '02'
oa: 1
oa_version: Preprint
page: '30'
pmid: 1
publication_identifier:
  eissn:
  - 2693-5015
publication_status: submitted
publisher: Research Square
status: public
title: WDFY3 cell autonomously controls neuronal migration
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: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...