Identification of signaling pathways that specify a subset of migrating enteric neural crest cells at the wavefront in mouse embryos

Dev Cell. 2024 Apr 15:S1534-5807(24)00202-8. doi: 10.1016/j.devcel.2024.03.034. Online ahead of print.ABSTRACTDuring enteric nervous system (ENS) development, pioneering wavefront enteric neural crest cells (ENCCs) initiate gut colonization. However, the molecular mechanisms guiding their specification and niche interaction are not fully understood. We used single-cell RNA sequencing and spatial transcriptomics to map the spatiotemporal dynamics and molecular landscape of wavefront ENCCs in mouse embryos. Our analysis shows a progressive decline in wavefront ENCC potency during migration and identifies transcription factors governing their specification and differentiation. We further delineate key signaling pathways (ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1) utilized by wavefront ENCCs to interact with their surrounding cells. Disruptions in these pathways are observed in human Hirschsprung's disease gut tissue, linking them to ENS malformations. Additionally, we observed region-specific and cell-type-specific transcriptional changes in surrounding gut tissues upon wavefront ENCC arrival, suggesting their role in shaping the gut microenvironment. This work offers a roadmap of ENS development, with implications for understanding ENS disorders.PMID:38636517 | DOI:10.1016/j.devcel.2024.03.034

Source: Developmental Cell - April 18, 2024 Category: Cytology Authors: Bingyan Zhou Chenzhao Feng Song Sun Xuyong Chen Didi Zhuansun Di Wang Xiaosi Yu Xinyao Meng Jun Xiao Luyao Wu Jing Wang Jing Wang Ke Chen Zejian Li Jingyi You Handan Mao Shimin Yang Jiaxin Zhang Chunlei Jiao Zhi Li Donghai Yu Xiaojuan Wu Tianqi Zhu Jixin Source Type: research