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Nerves play important roles in organ development and tissue homeostasis. Stem/progenitor cells differentiate into different cell lineages responsible for building the craniofacial organs. The mechanism by which nerves regulate stem/progenitor cell behavior in organ morphogenesis has not yet been comprehensively explored. Here, we use tooth root development in mouse as a model to investigate how sensory nerves regulate organogenesis. We show that sensory nerve fibers are enriched in the dental papilla at the initiation of tooth root development. Through single cell RNA-sequencing analysis of the trigeminal ganglion and developing molar, we reveal several signaling pathways that connect the sensory nerve with the developing molar, of which FGF signaling appears to be one of the important regulators. Fgfr2 is expressed in the progenitor cells during tooth root development. Loss of FGF signaling leads to shortened roots with compromised proliferation and differentiation of progenitor cells. Furthermore, Hh signaling is impaired in Gli1-CreER;Fgfr2fl/fl mice. Modulation of Hh signaling rescues the tooth root defects in these mice. Collectively, our findings elucidate the nerve-progenitor crosstalk and reveal the molecular mechanism of the FGF-SHH signaling cascade during tooth root morphogenesis. © 2024. Published by The Company of Biologists Ltd.

Citation

Fei Pei, Li Ma, Tingwei Guo, Mingyi Zhang, Junjun Jing, Quan Wen, Jifan Feng, Jie Lei, Jinzhi He, Eva Janečková, Thach-Vu Ho, Jian-Fu Chen, Yang Chai. Sensory nerve regulates progenitor cells via FGF-SHH axis in tooth root morphogenesis. Development (Cambridge, England). 2024 Jan 15;151(2)

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PMID: 38108472

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