Linking the environment, DAF-7/TGFβ signaling and LAG-2/DSL ligand expression in the germline stem cell niche

Abstract

The developmental accumulation of proliferative germ cells in the <i>C. elegans</i> hermaphrodite is sensitive to the organismal environment. Previously, we found that the TGFβ signaling pathway links the environment and proliferative germ cell accumulation. Neuronal DAF-7/TGFβ causes a DAF-1/TGFβR signaling cascade in the gonadal distal tip cell (DTC), the germline stem cell niche, where it negatively regulates a DAF-3 SMAD and DAF-5 Sno-Ski. LAG-2, a founding DSL ligand family member, is produced in the DTC and activates the GLP-1/Notch receptor on adjacent germ cells to maintain germline stem cell fate. Here, we show that DAF-7/TGFβ signaling promotes expression of <i>lag-2</i> in the DTC in a <i>daf-3-</i>dependent manner. Using ChIP and one-hybrid assays, we find evidence for direct interaction between DAF-3 and the <i>lag-2</i> promoter. We further identify a 25 bp DAF-3 binding element required for the DTC <i>lag-2</i> reporter response to the environment and to DAF-7/TGFβ signaling. Our results implicate DAF-3 repressor complex activity as a key molecular mechanism whereby the environment influences DSL ligand expression in the niche to modulate developmental expansion of the germline stem cell pool.