Dopey2 and Pcdh7 Orchestrate Brain Size and Architecture in Zebrafish Embryo

DOPEY2 has been shown to be associated with Down Syndrome and PCDH7 might be involved in Rett syndrome and MECP2 duplication syndrome. The mechanism as to 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, while 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.Funding Information: The authors gratefully acknowledge support from The National Key Research and Development Program of China (2018YFA0801005), the 1.3.5 project for disciplines of excellence of West China Hospital (ZYGD20007, ZYJC18011) Declaration of Interests: Authors declare that they have no competing interests.