Ciliary Protein Kif7 Regulates Gli and Ezh2 for Initiating the Neuronal Differentiation of Enteric Neural Crest Cells During Development

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2021 Oct 13

PMID 34644112

Citations 3

Authors

Frank Pui-Ling Lai

Zhixin Li

Tingwen Zhou

Adrian On Wah Leung

Sin-Ting Lau

Kathy Nga-Chu Lui

William Yu-Ming Wong

Pak-Chung Sham

Chi-Chung Hui

Elly Sau-Wai Ngan

Affiliations

Soon will be listed here.

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 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, inhibits Gli2 in enteric NCCs (ENCCs), where Gli2 positively regulates the expression of Ezh2 by inhibiting the -mediated suppression. In developing ENCCs, Ezh2 is a master regulator of 102 core genes underlying ENCC differentiation. Deletion of or inhibition of Ezh2 favors the neurogenic lineage differentiation of mouse and human ENCCs and rescues the ENS defects of 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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