Dopey2 and Pcdh7 orchestrate the development of embryonic neural stem cells/ progenitors in zebrafish
Yue Xiao,
Min Hu,
Qiyan Lin,
Ting Zhang,
Siying Li,
Linjuan Shu,
Xiuli Song,
Xiaoyong Xu,
Wentong Meng,
Xue Li,
Hong Xu,
Xianming Mo
Affiliations
Yue Xiao
Department of Pediatric Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Min Hu
Department of Pediatric Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Qiyan Lin
Department of Pediatric Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Ting Zhang
Department of Pediatric Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Siying Li
Department of Pediatric Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Linjuan Shu
Department of Pediatric Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Xiuli Song
Hangzhou HuaAn Biotechnology Co.Ltd, Hangzhou, China
Xiaoyong Xu
Hangzhou HuaAn Biotechnology Co.Ltd, Hangzhou, China
Wentong Meng
Department of Pediatric Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Xue Li
Department of Pediatric Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Hong Xu
Department of Pediatric Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Xianming Mo
Department of Pediatric Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China; Corresponding author
Summary: DOPEY2 has been shown to be associated with Down syndrome and PCDH7 might be involved in Rett syndrome and MECP2 duplication syndrome. The mechanism how both proteins play roles in these syndromes are largely unknown. Here, we show that Dopey2 and Pcdh7 balance the proliferation and differentiation of neural stem cells and progenitors during embryonic neurogenesis to generate proper size and architecture of zebrafish brains. Dopey2 and Pcdh7 mutually restricted expression of each other in zebrafish embryos. Dopey2 was responsible for the proliferation of neural stem cells/progenitors, whereas Pcdh7 was responsible for the differentiation of neural stem cells/progenitors. Both proteins were shown to orchestrate the proper development and arrangement of neural cells in zebrafish embryonic brains. The results provide an insight into mechanisms to understand how the embryonic brain is constituted and how developmental defects occur in the brains of patients with Down syndrome, Rett syndrome, or MECP2 duplication syndrome.