Document Detail

Cyclin E controls Drosophila female germline stem cell maintenance independently of its role in proliferation by modulating responsiveness to niche signals.
MedLine Citation:
PMID:  23293285     Owner:  NLM     Status:  MEDLINE    
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.
Elizabeth T Ables; Daniela Drummond-Barbosa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  140     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-03-07     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  530-40     Citation Subset:  IM    
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MeSH Terms
Cell Division
Cell Proliferation*
Cyclin B / genetics,  metabolism
Cyclin E / genetics,  metabolism*
Cyclin-Dependent Kinase 2 / genetics,  metabolism
Drosophila / cytology*,  metabolism
Drosophila Proteins / genetics,  metabolism
G2 Phase
Germ Cells / cytology,  metabolism
Green Fluorescent Proteins / metabolism
Intercellular Junctions / genetics,  metabolism
Signal Transduction
Stem Cell Niche*
Stem Cells / cytology*,  metabolism
Grant Support
Reg. No./Substance:
0/CycB protein, Drosophila; 0/Cyclin B; 0/Cyclin E; 0/Drosophila Proteins; 147336-22-9/Green Fluorescent Proteins; EC Kinase 2; EC protein, Drosophila

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