The Role And Mechanism Of Autism Risk Gene Tbr1 In Early Neurodevelopment And Axon Projection Of Zebrafish

Autism spectrum disorders(ASDs)is a widespread neurodevelopmental disorder.The core symptoms are social communication and interaction disorders,narrow interests,and repetitive stereotyped behaviors.For decades,people have tried to explain the essence of autism disorder,but so far its etiology and pathogenesis are still far from clear.So far,there is no specific medicine for the core symptoms of ASD.The etiology of ASD is complex.Genetic,immune,environmental factors,etc.are all related to the onset of autism.Among them,genetic factors are crucial to the onset of ASD,and more than a hundred risk genes have been discovered.TBR1 is one of the high-confidence risk genes for autism.It controls the transcriptional cascade associated with the onset of ASD.Mutations in this gene in mice lead to autistic behaviors,showing abnormal axon connections and behaviors,but development in the process,its role and mechanism in axon growth and guidance are still poorly understood.Our previous studies have found that zebrafish with tbr1 gene mutations exhibit autistic behaviors and abnormalities in the anterior telomere junction during early development.This project further explores the mechanism of abnormal brain connectivity and found that the dorsal telomere neurons of the zebrafish proliferate reduced and affected the expression of Wnt signaling ligands in the Wnt signaling pathway and target genes downstream of the Wnt signaling pathway during early development.After treating the embryos with lithium chloride,a Wnt signaling pathway agonist,it was found that lithium chloride can rescue the tbr1 b mutation defects in the anterior joint connection of somatic zebrafish embryos.In addition,the expression of CRMP family genes of downstream axon guidance factor genes in tbr1 mutants was also affected.Finally,through behavioral analysis,it is found that zebrafish juveniles show behavioral abnormalities,which may be related to abnormal brain connections in the early stage.This project preliminarily studies the molecular mechanism of brain connection defects in autism models,and provides an experimental basis for in-depth study of the pathogenesis of autism and exploration of prevention and treatment methods.