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 journalArticlepeer-review

53 Scopus citations


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
StatePublished - Sep 8 2014

ASJC Scopus subject areas

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


Dive into the research topics of 'Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology'. Together they form a unique fingerprint.

Cite this