Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology

Lori A. Orosco, Adam P. Ross, Staci L. Cates, Sean E. Scott, Dennis Wu, Jiho Sohn, David E Pleasure, Samuel J. Pleasure, Iannis Adamopoulos, Konstantinos Zarbalis

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic aetiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs. Loss of Wdfy3 leads to a regionally enlarged cerebral cortex resembling early brain overgrowth described in many children on the autism spectrum. In addition, affected mouse mutants display migration defects of cortical projection neurons, a recognized cause of epilepsy, which is significantly comorbid with autism. Our analysis of affected mouse mutants defines an important role for Wdfy3 in regulating neural progenitor divisions and neural migration in the developing brain. Furthermore, Wdfy3 is essential for cerebral expansion and functional organization while its loss-of-function results in pathological changes characteristic of ASDs.

Original languageEnglish (US)
Article number5692
JournalNature Communications
Volume5
DOIs
StatePublished - Sep 8 2014

Fingerprint

Neurogenesis
pathology
Pathology
Autistic Disorder
mice
Brain
Defects
disorders
Neurons
Genes
brain
Developmental Disabilities
cerebral cortex
epilepsy
etiology
disabilities
Cerebral Cortex
defects
Epilepsy
neurons

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology. / Orosco, Lori A.; Ross, Adam P.; Cates, Staci L.; Scott, Sean E.; Wu, Dennis; Sohn, Jiho; Pleasure, David E; Pleasure, Samuel J.; Adamopoulos, Iannis; Zarbalis, Konstantinos.

In: Nature Communications, Vol. 5, 5692, 08.09.2014.

Research output: Contribution to journalArticle

Orosco, Lori A. ; Ross, Adam P. ; Cates, Staci L. ; Scott, Sean E. ; Wu, Dennis ; Sohn, Jiho ; Pleasure, David E ; Pleasure, Samuel J. ; Adamopoulos, Iannis ; Zarbalis, Konstantinos. / Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology. In: Nature Communications. 2014 ; Vol. 5.
@article{9770a81acb934df0a7398f36f6f994e7,
title = "Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology",
abstract = "Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic aetiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs. Loss of Wdfy3 leads to a regionally enlarged cerebral cortex resembling early brain overgrowth described in many children on the autism spectrum. In addition, affected mouse mutants display migration defects of cortical projection neurons, a recognized cause of epilepsy, which is significantly comorbid with autism. Our analysis of affected mouse mutants defines an important role for Wdfy3 in regulating neural progenitor divisions and neural migration in the developing brain. Furthermore, Wdfy3 is essential for cerebral expansion and functional organization while its loss-of-function results in pathological changes characteristic of ASDs.",
author = "Orosco, {Lori A.} and Ross, {Adam P.} and Cates, {Staci L.} and Scott, {Sean E.} and Dennis Wu and Jiho Sohn and Pleasure, {David E} and Pleasure, {Samuel J.} and Iannis Adamopoulos and Konstantinos Zarbalis",
year = "2014",
month = "9",
day = "8",
doi = "10.1038/ncomms5692",
language = "English (US)",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology

AU - Orosco, Lori A.

AU - Ross, Adam P.

AU - Cates, Staci L.

AU - Scott, Sean E.

AU - Wu, Dennis

AU - Sohn, Jiho

AU - Pleasure, David E

AU - Pleasure, Samuel J.

AU - Adamopoulos, Iannis

AU - Zarbalis, Konstantinos

PY - 2014/9/8

Y1 - 2014/9/8

N2 - Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic aetiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs. Loss of Wdfy3 leads to a regionally enlarged cerebral cortex resembling early brain overgrowth described in many children on the autism spectrum. In addition, affected mouse mutants display migration defects of cortical projection neurons, a recognized cause of epilepsy, which is significantly comorbid with autism. Our analysis of affected mouse mutants defines an important role for Wdfy3 in regulating neural progenitor divisions and neural migration in the developing brain. Furthermore, Wdfy3 is essential for cerebral expansion and functional organization while its loss-of-function results in pathological changes characteristic of ASDs.

AB - Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic aetiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs. Loss of Wdfy3 leads to a regionally enlarged cerebral cortex resembling early brain overgrowth described in many children on the autism spectrum. In addition, affected mouse mutants display migration defects of cortical projection neurons, a recognized cause of epilepsy, which is significantly comorbid with autism. Our analysis of affected mouse mutants defines an important role for Wdfy3 in regulating neural progenitor divisions and neural migration in the developing brain. Furthermore, Wdfy3 is essential for cerebral expansion and functional organization while its loss-of-function results in pathological changes characteristic of ASDs.

UR - http://www.scopus.com/inward/record.url?scp=84943528737&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84943528737&partnerID=8YFLogxK

U2 - 10.1038/ncomms5692

DO - 10.1038/ncomms5692

M3 - Article

C2 - 25198012

AN - SCOPUS:84943528737

VL - 5

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 5692

ER -