The Role And Mechanism Of Autism High Risk Gene Chd8 In The Development Of Enteric Nervous System

Gastrointestinal disorders is often associated with Autism Spectrum Disorder,a neurodevelopmental disorder,and is associated with the severity of autism,but the correlation mechanism between the two has not been elucidated.CHD8 is one of the high-risk genes for autism.Nearly 90% of patients with this gene mutation have autism,and about 80% of them have gastrointestinal disorders.Taking zebrafish as experimental animals,our previous studies showed that chd8 was highly expressed in the developing intestinal tract before the intestinal neural crest cells had migrated into the intestinal tract.chd8 knockdown in single-cell period resulted in the reduction of intestinal neurons,and chd8 knockdown resulted in the abnormal development of intestinal epithelium.In my later research,it was found that knocking-down chd8 during the single-cell period slowed down the frequency of intestinal peristalsis,and the differentiation of intestinal neuron subtypes also epithelial cells was influenced.Using in situ hybridization I found the expression level of mesodermal-derived smooth muscle cells marker was decreased.We believe that chd8 plays an important role in the early development of intestinal epithelium,providing an appropriate micro-environment for the recruitment of intestinal neural crest cells migrated from the ectoderm and mesoderm derived smooth muscle cells into the intestinal tract,so as to regulate the development and function of the overall intestinal tract,which may further affect the overall development through factors such as the gut-brain axis.