WD　repeat　domain　62　(WDR62)　was　identified　as　the　second　most　causative　gene　of　autosomal　recessive　primary　microcephaly　(MCPH)　frequently　associated　structural　abnormalities　such　as　lissencephaly,　polymicrogyria　as　well　as　hypoplasia　of　the　corpus　callosum,　however,　underlining　mechanism　behind　these　abnormality　remains　unknown.　Here　we　show　that　either　ablation　of　WDR62　in　neural　progenitor　cells　(NPCs)　or　post-mitotic　neurons　both　impedes　cortical　neuronal　radial　migration　in　the　developing　brain.　WDR62　modulates　the　transition　from　multipolar　to　bipolar　states　in　migrating　neurons　and　ensures　the　accurate　formation　of　contralateral　projections　of　callosal　neurons.　Our　results　further　indicated　that　ASD-related　mutations　in　WDR62　are　associated　with　a　reduced　capacity　for　neuronal　migration　in　the　developing　brain.　Finally,　we　provide　the　molecular　evidence　that　the　levels　of　Reelin,　a　key　modulator　of　neuronal　migration　and　high　confidence　ASD　candidate　gene,　were　significantly　reduced　in　the　brains　of　Wdr62　deficient　mice.　These　finding　define　critical　roles　for　WDR62　in　cortical　neuronal　radial　migration　and　callosal　projection　which　provides　insights　into　the　pathogenesis　of　WDR62　deficiency-related　brain　dysplasia.　©　2024