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Control of multiciliogenesis by miR-34/449 in the male reproductive tract through enforcing cell cycle exit

Authors :
Fu-Rong Bai
Yue Liu
Jingwen Wu
Yu-Jie Wu
Chen Xu
Li Wang
Yanqin Hu
Source :
Journal of Cell Science, article-version (VoR) Version of Record
Publication Year :
2021
Publisher :
The Company of Biologists, 2021.

Abstract

Multiciliated cells (MCCs) are terminally differentiated postmitotic cells that possess hundreds of motile cilia on their apical surface. Defects in cilia formation are associated with ciliopathies that affect many organs. In this study, we tested the role and mechanism of the miR-34/449 family in the regulation of multiciliogenesis in EDs using an miR-34b/cāˆ’/āˆ’; miR-449āˆ’/āˆ’ double knockout (dKO) mouse model. MiR-34b/c and miR-449 depletion led to a reduced number of MCCs and abnormal cilia structure in the EDs starting from postnatal day (P)14. However, abnormal MCC differentiation in the dKO EDs could be observed as early as P7. RNA-seq analyses revealed that the aberrant development of MCCs in the EDs of dKO mice was associated with the upregulation of genes involved in cell cycle control. Using a cyclin-dependent kinase inhibitor to force cell cycle exit promoted MCC differentiation, and partially rescued the defective multiciliogenesis in the EDs of dKO mice. Taken together, our results suggest that miR-34b/c and miR-449 play an essential role in multiciliogenesis in EDs by regulating cell cycle exit.<br />Summary: Mutagenic, expression and histological analyses reveal an essential role for miR-34b/c and miR-449 in multiciliogenesis in efferent ductules of the male reproductive tract by regulating cell cycle exit.

Details

ISSN :
14779137 and 00219533
Volume :
134
Database :
OpenAIRE
Journal :
Journal of Cell Science
Accession number :
edsair.doi.dedup.....20f12ceb80095d1f1ea01ac144e3a449
Full Text :
https://doi.org/10.1242/jcs.253450