Wnt signaling and CEH-22/tinman/Nkx2.5 specify a stem cell niche in C. elegans.
Wnt signaling regulates many aspects of metazoan development, including stem cells. In C. elegans, Wnt/MAPK signaling controls asymmetric divisions. A recent model proposed that the POP-1/TCF DNA binding protein works together with SYS-1/beta-catenin to activate transcription of target genes in response to Wnt/MAPK signaling. 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. No DTCs are produced in the absence of POP-1/TCF or SYS-1/beta-catenin, and extra DTCs are made upon overexpression of SYS-1/beta-catenin. Here we report that POP-1/TCF and SYS-1/beta-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.
Lam
Ngan
N
Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Chesney
Michael A
MA
Kimble
Judith
J
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000196:embryology; D006609:High Mobility Group Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism
C109217:CEH-22 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; C502083:Sys-1 protein, C elegans; D014157:Transcription Factors; D051153:Wnt Proteins; C096787:pop-1 protein, C elegans; D008156:Luciferases