Developmental cell · 2024
Identification of signaling pathways that specify a subset of migrating enteric neural crest cells at the wavefront in mouse embryos.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Zhou Bingyan, Feng Chenzhao, Sun Song, Chen Xuyong, Zhuansun Didi, Wang Di, Yu Xiaosi, Meng Xinyao, Xiao Jun, Wu Luyao, Wang Jing, Wang Jing, Chen Ke, Li Zejian, You Jingyi, Mao Handan, Yang Shimin, Zhang Jiaxin, Jiao Chunlei, Li Zhi, Yu Donghai, Wu Xiaojuan, Zhu Tianqi, Yang Jixin, Xiang Lei, Liu Jiazhe, Chai Tailiang, Shen Juan, Mao Chuan-Xi, Hu Juncheng, Hao Xingjie, Xiong Bo, Zheng Shan, Liu Zhihua, Feng Jiexiong
Аннотация
During 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.