RRC ID 55875
Author Furuta T, Joo HJ, Trimmer KA, Chen SY, Arur S.
Title GSK-3 promotes S-phase entry and progression in C. elegans germline stem cells to maintain tissue output.
Journal Development
Abstract Adult C. elegans germline stem cells (GSCs) and mouse embryonic stem cells (mESCs) exhibit a non-canonical cell cycle structure with an abbreviated G1 phase and phase-independent expression of Cdk2 and cyclin E. Mechanisms that promote the abbreviated cell cycle remain unknown, as do the consequences of not maintaining an abbreviated cell cycle in these tissues. In GSCs, we discovered that loss of gsk-3 results in reduced GSC proliferation without changes in differentiation or responsiveness to GLP-1/Notch signaling. We find that DPL-1 transcriptional activity inhibits CDK-2 mRNA accumulation in GSCs, which leads to slower S-phase entry and progression. Inhibition of dpl-1 or transgenic expression of CDK-2 via a heterologous germline promoter rescues the S-phase entry and progression defects of the gsk-3 mutants, demonstrating that transcriptional regulation rather than post-translational control of CDK-2 establishes the abbreviated cell cycle structure in GSCs. This highlights an inhibitory cascade wherein GSK-3 inhibits DPL-1 and DPL-1 inhibits cdk-2 transcription. Constitutive GSK-3 activity through this cascade maintains an abbreviated cell cycle structure to permit the efficient proliferation of GSCs necessary for continuous tissue output.
Volume 145(10)
Published 2018-5-14
DOI 10.1242/dev.161042
PII dev.161042
PMID 29695611
PMC PMC6001380
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / embryology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cell Differentiation / genetics Cell Proliferation / genetics Cyclin E / biosynthesis Cyclin-Dependent Kinase 2 / biosynthesis* Cyclin-Dependent Kinase 2 / genetics Germ Cells / cytology* Glycogen Synthase Kinase 3 / genetics Glycogen Synthase Kinase 3 / metabolism* RNA Interference RNA, Messenger / genetics RNA, Small Interfering / genetics Receptors, Notch / metabolism S Phase / physiology* Signal Transduction / genetics Stem Cells / cytology* Transcription Factors / genetics* Transcription, Genetic / genetics
IF 5.763
Times Cited 5
C.elegans tm2223