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Control of multiciliogenesis by miR-34/449 in the male reproductive tract through enforcing cell cycle exit
- 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/cā/ā; miR-449ā/ā 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.
- Subjects :
- Male
Multiciliogenesis
Male reproductive tract
Biology
Ciliopathies
Mice
03 medical and health sciences
Cilia and Flagella
0302 clinical medicine
Downregulation and upregulation
Animals
Cilia
Gene
030304 developmental biology
Motile cilia
0303 health sciences
Kinase
Cilium
Cell Cycle
Cell Differentiation
Cell Biology
Cell cycle
miR-34/449
Cell biology
MicroRNAs
Motile cilium
Cell Division
030217 neurology & neurosurgery
Research Article
Subjects
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