The Role Of Autism Spectrum Disorder Risk Gene CTNND2 In Early Neural Development

Autism Spectrum Disorder(ASD)is a kind of heritable extensive neurological development disorder,the ASD patients got the core symptoms of repeat stereotyped behavior,impairments in reciprocal social interaction and communication.The nosogenesis and pathogenesis of ASD are unknown now,and there is no medicine and treatment could healing ASD core symptoms.Many factors could lead to ASD,such as inheritance,environment,immune,and inflammation.ASD is an high-heritable disorder,more than 100 genes are found related to ASD,and CTNND2 is a risk gene of autism,it specifically express high-level in human and rat brain structure at very early development stage.Many studies show CTNND2 helps neural cell maintain morphology and related to synaptogenesis,but the function of CTNND2 in neuron early development is unknown.This study used zebrafish as model and knockdown ctnnd2 b gene by morpholino,and shows ctnnd2 b knockdown leads to notochord twist and axis bending,and influence the WNT signaling protein WNT3 a and AXIN2 expression.It also hints the abnormal development of Purkinje cell in cerebellum.The knockdown larva exhibits aberrant behavior such as decrease of move distance and reduced tendency to exploration at 5dpf to 7dpf.Our results may help to explain the early neuron development disorder in ASD patient,and support the key role of WNT signaling pathway in ASD.This study provides a novel idea of CTNND2 mutation related to ASD,and expand sights of CTNND2 study.