title: Wnt signaling and CEH-22/tinman/Nkx2.5 specify a stem cell niche in C. elegans.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Ngan
authors.initials: N
authors.lastname: Lam
authors.forename: Michael A
authors.initials: MA
authors.lastname: Chesney
authors.forename: Judith
authors.initials: J
authors.lastname: Kimble
mesh_terms: 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
chemical_list: 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