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.