RRC ID 70843
Author Takemura M, Bowden N, Lu YS, Nakato E, O'Connor MB, Nakato H.
Title Drosophila MOV10 regulates the termination of midgut regeneration.
Journal Genetics
Abstract The molecular mechanisms by which stem cell proliferation is precisely controlled during the course of regeneration are poorly understood. Namely, how a damaged tissue senses when to terminate the regeneration process, inactivates stem cell mitotic activity, and organizes ECM integrity remain fundamental unanswered questions. The Drosophila midgut intestinal stem cell (ISC) offers an excellent model system to study the molecular basis for stem cell inactivation. Here, we show that a novel gene, CG6967 or dMOV10, is induced at the termination stage of midgut regeneration, and shows an inhibitory effect on ISC proliferation. dMOV10 encodes a putative component of the microRNA (miRNA) gene silencing complex (miRISC). Our data, along with previous studies on the mammalian MOV10, suggest that dMOV10 is not a core member of miRISC, but modulates miRISC activity as an additional component. Further analyses identified direct target mRNAs of dMOV10-containing miRISC, including Daughter against Dpp (Dad), a known inhibitor of BMP/TGF-β signaling. We show that RNAi knockdown of Dad significantly impaired ISC division during regeneration. We also identified six miRNAs that are induced at the termination stage and their potential target transcripts. One of these miRNAs, mir-1, is required for proper termination of ISC division at the end of regeneration. We propose that miRNA-mediated gene regulation contributes to the precise control of Drosophila midgut regeneration.
Volume 218(1)
Published 2021-5-17
DOI 10.1093/genetics/iyab031
PII 6156853
PMID 33693718
PMC PMC8128384
MeSH Animals Cell Differentiation / genetics Cell Proliferation / genetics Cell Self Renewal / genetics Drosophila / genetics Drosophila / metabolism Drosophila / physiology* Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila Proteins / physiology Enterocytes / cytology Intestinal Mucosa / cytology* Intestines / cytology MicroRNAs / genetics MicroRNAs / metabolism RNA Helicases RNA-Induced Silencing Complex / genetics RNA-Induced Silencing Complex / metabolism Regeneration / physiology* Signal Transduction Stem Cells / cytology* Stem Cells / metabolism
IF 4.015
Drosophila DGRC#113886 DGRC#112001 DGRC#108851 DGRC#110807