Ciliary protein Kif7 regulates Gli and Ezh2 for initiating the neuronal differentiation of enteric neural crest cells during development

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Abstract

Gastrointestinal motility disorders occur frequently in patients with ciliopathy, but the underlying genetic link is unclear. The ciliary protein Kif7 can positively or negatively regulate Hedgehog signaling in different cellular contexts. Mice with neural crest cell (NCC)–specific Kif7 deficiency show a marked reduction of enteric NOS+ inhibitory neurons. Malformation of enteric nervous system (ENS) causes growth retardation and gut motility defect in mice. Mechanistically, Kif7 inhibits Gli2 in enteric NCCs (ENCCs), where Gli2 positively regulates the expression of Ezh2 by inhibiting the miR124-mediated suppression. In developing ENCCs, Ezh2 is a master regulator of 102 core genes underlying ENCC differentiation. Deletion of Gli2 or inhibition of Ezh2 favors the neurogenic lineage differentiation of mouse and human ENCCs and rescues the ENS defects of Kif7 mutants. In summary, Hedgehog signal, via Kif7-Gli-Ezh2, controls the timely expressions of the core genes to mediate the differentiation of ENCCs.

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APA

Lai, F. P. L., Li, Z., Zhou, T., Leung, A. O. W., Lau, S. T., Lui, K. N. C., … Ngan, E. S. W. (2021). Ciliary protein Kif7 regulates Gli and Ezh2 for initiating the neuronal differentiation of enteric neural crest cells during development. Science Advances, 7(42). https://doi.org/10.1126/sciadv.abf7472

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