Notch signaling plays critical roles in patterning metazoan development. In Caenorhabditis elegans, precise regulation of GLP-1 Notch receptor expression is important for development of the C. elegans germline. GLP-1 loss results in sterility whereas overexpression causes germline tumour formation. We have identified a regulatory mechanism where glp-1 transcription is controlled by a calcium-dependent AP transcription factor (TF) to maintain germline stem cell number.
Using in silico analysis and in vivo CRISPR-Cas9 genome editing, we identified a functional, and highly conserved, AP TF DNA binding motif in the glp-1 promoter. AP TFs factors are known to be regulated by intracellular Ca2+ levels in mammals. In concurrence, we found that Ca2+ also drives the interaction between the AP TF and glp-1 promoter in worms. We previously showed that the absence of syndecan causes elevated cytosolic Ca2+ levels through dysregulation of TRP Ca2+ channels. Our current research shows that the reduction of germline stem cell number caused by loss of SDN-1 is rescued by removal of the TRP-2 channel. We found that this SDN-1/TRP-2 axis is required for AP TF regulation of glp-1 expression in the germline. Hence, our work identifies a novel regulatory mechanism that regulates germline stem cell development by controlling Notch receptor transcription.