The Role Of Autism High Risk Gene Chd8 In Intestine Development

Autism spectrum disorder(ASD)is a kind of extensive neurological development disorder.In addition to core symptoms,patients often accompanied with comorbidities,in which gastrointestinal problem(GI problem)is rather obvious.ASD patients are more likely to suffer from gastrointestinal problem clinically,such as diarrhea,constipation,abdominal pain,enteritis and so on.These symptoms are closely related to emotional disorders and behavioral problems of patients.Therapeutics for GI problem in ASD patients is helpful to relieve the core symptoms of patients.As an autism high risk gene,chromo-domain helicase DNA-binding protein 8(CHD8)plays an important role in multiple neural development processes.Because of the high incidence of GI problem in ASD patients especially in patients with CHD8 mutation,and gut-brain axis theory of the close relationship between gut and brain,we use zebrafish as a model to explore the role of chd8 in intestine development,aiming to partially explain the possible causes of GI problem observed in ASD patients and possible association between gastrointestinal symptoms and central nervous system symptoms.Our results show that chd8 has a high expression in the gut during early development of zebrafish,and after knocking down the expression of chd8 zebrafish show intestinal motility defects.Research of multiple cells having significant influence on intestine function suggest that chd8 plays an important role in the development of enteric neuron,goblet cell and endocrine cell.Our results are the first study to reveal the role of chd8 in early intestinal development.Meanwhile,the results of this study may help to explain the occurrence of GI problem in ASD patient,that is to say some of the GI problem in ASD patients may be due to the mutation of autism high risk gene which also has a role in intestinal development.Our research explain the possible causes of GI problem in patients with CHD8 mutation from a perspective of development,and the purpose of this study is to provide a theoretical basis for the treatment of GI problem in ASD patients.