RRC ID 46006
Author Kershner AM, Shin H, Hansen TJ, Kimble J.
Title Discovery of two GLP-1/Notch target genes that account for the role of GLP-1/Notch signaling in stem cell maintenance.
Journal Proc Natl Acad Sci U S A
Abstract A stem cell's immediate microenvironment creates an essential "niche" to maintain stem cell self-renewal. Many niches and their intercellular signaling pathways are known, but for the most part, the key downstream targets of niche signaling remain elusive. Here, we report the discovery of two GLP-1/Notch target genes, lst-1 (lateral signaling target) and sygl-1 (synthetic Glp), that function redundantly to maintain germ-line stem cells (GSCs) in the nematode Caenorhabditis elegans. Whereas lst-1 and sygl-1 single mutants appear normal, lst-1 sygl-1 double mutants are phenotypically indistinguishable from glp-1/Notch mutants. Multiple lines of evidence demonstrate that GLP-1/Notch signaling activates lst-1 and sygl-1 expression in GSCs within the niche. Therefore, these two genes fully account for the role of GLP-1/Notch signaling in GSC maintenance. Importantly, lst-1 and sygl-1 are not required for GLP-1/Notch signaling per se. We conclude that lst-1 and sygl-1 forge a critical link between Notch signaling and GSC maintenance.
Volume 111(10)
Pages 3739-44
Published 2014-3-11
DOI 10.1073/pnas.1401861111
PII 1401861111
PMID 24567412
PMC PMC3956202
MeSH Benzimidazoles Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Gene Expression Regulation / genetics Gene Expression Regulation / physiology Glucagon-Like Peptide 1 / genetics Glucagon-Like Peptide 1 / metabolism* Immunohistochemistry In Situ Hybridization Polysorbates RNA Interference Receptors, Notch / metabolism* Signal Transduction / physiology* Stem Cells / physiology*
IF 9.412
Times Cited 38
C.elegans tm5040