RRC ID 28869
Author Ables ET, Drummond-Barbosa D.
Title Cyclin E controls Drosophila female germline stem cell maintenance independently of its role in proliferation by modulating responsiveness to niche signals.
Journal Development
Abstract Stem cells must proliferate while maintaining 'stemness'; however, much remains to be learned about how factors that control the division of stem cells influence their identity. Multiple stem cell types display cell cycles with short G1 phases, thought to minimize susceptibility to differentiation factors. Drosophila female germline stem cells (GSCs) have short G1 and long G2 phases, and diet-dependent systemic factors often modulate G2. We previously observed that Cyclin E (CycE), a known G1/S regulator, is atypically expressed in GSCs during G2/M; however, it remained unclear whether CycE has cell cycle-independent roles in GSCs or whether it acts exclusively by modulating the cell cycle. In this study, we detected CycE activity during G2/M, reflecting its altered expression pattern, and showed that CycE and its canonical partner, Cyclin-dependent kinase 2 (Cdk2), are required not only for GSC proliferation, but also for GSC maintenance. In genetic mosaics, CycE- and Cdk2-deficient GSCs are rapidly lost from the niche, remain arrested in a G1-like state, and undergo excessive growth and incomplete differentiation. However, we found that CycE controls GSC maintenance independently of its role in the cell cycle; GSCs harboring specific hypomorphic CycE mutations are not efficiently maintained despite normal proliferation rates. Finally, CycE-deficient GSCs have an impaired response to niche bone morphogenetic protein signals that are required for GSC self-renewal, suggesting that CycE modulates niche-GSC communication. Taken together, these results show unequivocally that the roles of CycE/Cdk2 in GSC division cycle regulation and GSC maintenance are separable, and thus potentially involve distinct sets of phosphorylation targets.
Volume 140(3)
Pages 530-40
Published 2013-2-1
DOI 10.1242/dev.088583
PII 140/3/530
PMID 23293285
PMC PMC3561789
MeSH Alleles Animals Apoptosis Cell Division Cell Proliferation* Cyclin B / genetics Cyclin B / metabolism Cyclin E / genetics Cyclin E / metabolism* Cyclin-Dependent Kinase 2 / genetics Cyclin-Dependent Kinase 2 / metabolism Drosophila / cytology* Drosophila / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism Female G2 Phase Germ Cells / cytology Germ Cells / metabolism Green Fluorescent Proteins / metabolism Intercellular Junctions / genetics Intercellular Junctions / metabolism Mutation Phenotype Signal Transduction Stem Cell Niche* Stem Cells / cytology* Stem Cells / metabolism
IF 5.611
Times Cited 34
Drosophila DGRC#111513