Wnt Signaling and CEH-22/tinman/Nkx2.5 Specify a Stem Cell Niche in C. elegans

SummaryWnt signaling regulates many aspects of metazoan development, including stem cells 1, 2 and 3. In C. elegans, Wnt/MAPK signaling controls asymmetric divisions 4 and 5. A recent model proposed that the POP-1/TCF DNA binding protein works together with SYS-1/β-catenin to activate transcription of target genes in response to Wnt/MAPK signaling [6]. The somatic gonadal precursor (SGP) divides asymmetrically to generate distal and proximal daughters of distinct fates: only its distal daughter generates a distal tip cell (DTC), which is required for stem cell maintenance [7]. No DTCs are produced in the absence of POP-1/TCF or SYS-1/β-catenin, and extra DTCs are made upon overexpression of SYS-1/β-catenin 6, 8 and 9. Here we report that POP-1/TCF and SYS-1/β-catenin directly activate transcription of ceh-22/nkx2.5 isoforms in SGP distal daughters, a finding that confirms the proposed model of Wnt/MAPK signaling. In addition, we demonstrate that the CEH-22/Nkx2.5 homeodomain transcription factor is a key regulator of DTC specification. We speculate that these conserved molecular regulators of the DTC niche in nematodes may provide insight into specification of stem cell niches more broadly.