The EMB/ATG7-mediated autophagic process regulates neurite outgrowth and promotes enteric neuronal development
Abstract
The formation of the enteric nervous system (ENS) primarily involves the migration of enteric neural crest-derived cells (ENCCs) and the subsequent maturation of enteric neurons. The developmental dysfunction of ENCCs and enteric neurons can result in ENS disorders, such as hypoganglionosis (HG). Although neurite outgrowth is fundamental to neuronal maturation, the mechanisms by which neurite outgrowth influences neuronal maturation remain poorly defined. Here, we identified EMB as a critical regulator of enteric neuronal maturation. In EMB mutant patients, the expression of EMB is reduced in the enteric neurons of the HG-affected colon. In mice, knockdown of Emb exhibited HG-like features and defects. In vitro experiments, along with analyses using Smart-seq2 and immunoprecipitation-mass spectrometry, demonstrated that EMB is essential for autophagic flux and physically interacts with ATG7, recruiting it to the autophagosomal membrane to facilitate autophagosome formation, and then EMB/ATG7-mediated autophagy promotes neurite outgrowth. Our findings elucidate EMB-mediated autophagy as a pivotal pathway in regulating neurite outgrowth and promoting the maturation of enteric neurons, which provides a mechanistic basis for understanding ENS disorders.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (21)
Luyao Wu
School of Chemistry & Chemical Engineering
Jun Xiao
Xinyao Meng
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Jing Wang
Hunan Cancer Hospital Changsha China
Handan Mao
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Jingyi You
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Zejian Li
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Ke Chen
Qiong Wang
Bingyan Zhou
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Yingjian Chen
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Lei Xiang
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Xiaosi Yu
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Shimin Yang
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Jiaxin Zhang
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Didi Zhuansun
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Chunlei Jiao
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Di Wang
Jixin Yang
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Xuyong Chen
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Jiexiong Feng
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology