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.
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, California 95817, USA [2] Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, California 95817, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Orosco
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, California 95817, USA [2] Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, California 95817, USA.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Ross
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, California 95817, USA [2] Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, California 95817, USA.
authors.forename: Staci L
authors.initials: SL
authors.lastname: Cates
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, California 95817, USA [2] Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, California 95817, USA.
authors.forename: Sean E
authors.initials: SE
authors.lastname: Scott
authors.affiliation: 1] Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, California 95817, USA [2] Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California 95616, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Wu
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, California 95817, USA.
authors.forename: Jiho
authors.initials: J
authors.lastname: Sohn
authors.affiliation: 1] Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, California 95817, USA [2] Departments of Neurology and Pediatrics, University of California at Davis, Sacramento, California 95817, USA.
authors.forename: David
authors.initials: D
authors.lastname: Pleasure
authors.affiliation: Department of Neurology, Programs in Neuroscience, Developmental and Stem Cell Biology, UCSF Institute for Regeneration Medicine, University of California at San Francisco, Sandler Neurosciences Center, Box 3206, 675 Nelson Rising Lane, Room 214, San Francisco, California 94158, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Pleasure
authors.affiliation: 1] Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, California 95817, USA [2] Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, California 95616, USA.
authors.forename: Iannis E
authors.initials: IE
authors.lastname: Adamopoulos
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, California 95817, USA [2] Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, California 95817, USA.
authors.forename: Konstantinos S
authors.initials: KS
authors.lastname: Zarbalis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000071183:Autophagy-Related Proteins; D002465:Cell Movement / Q000235:genetics*; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D033921:Vesicular Transport Proteins; C496370:Wdfy3 protein, mouse