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Protruding vulva mutants identify novel loci and Wnt signaling factors that function during Caenorhabditis elegans vulva development.

Department of Developmental Biology, Stanford University, Stanford, California 94305, USA.
Genetics (Impact Factor: 4.87). 12/2000; 156(3):1097-116.
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ABSTRACT The Caenorhabditis elegans vulva develops from the progeny of three vulval precursor cells (VPCs) induced to divide and differentiate by a signal from the somatic gonad. Evolutionarily conserved Ras and Notch extracellular signaling pathways are known to function during this process. To identify novel loci acting in vulval development, we carried out a genetic screen for mutants having a protruding-vulva (Pvl) mutant phenotype. Here we report the initial genetic characterization of several novel loci: bar-1, pvl-4, pvl-5, and pvl-6. In addition, on the basis of their Pvl phenotypes, we show that the previously identified genes lin-26, mom-3/mig-14, egl-18, and sem-4 also function during vulval development. Our characterization indicates that (1) pvl-4 and pvl-5 are required for generation/survival of the VPCs; (2) bar-1, mom-3/mig-14, egl-18, and sem-4 play a role in VPC fate specification; (3) lin-26 is required for proper VPC fate execution; and (4) pvl-6 acts during vulval morphogenesis. In addition, two of these genes, bar-1 and mom-3/mig-14, are known to function in processes regulated by Wnt signaling, suggesting that a Wnt signaling pathway is acting during vulval development.

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Available from: David M Eisenmann, Sep 04, 2014
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    • "Wnt signaling is known to function in the specification or maintenance of the VPC fate, as well as in the asymmetric division of the VPCs P5.p and P7.p (Eisenmann et al. 1998; Eisenmann and Kim 2000; Gleason et al. 2002, 2006; Green et al. 2008). Abnormalities in vulval morphology observed at the L4 stage could indicate a defect in VPC fate specification or fate execution, vulval cell formation, or vulval morphogenesis (Eisenmann and Kim 2000). Of the 50 genes examined, five genes (cdk-4, cki-1, kin-10, mlt-11, and nhr-23) showed alterations in adult seam cell number (Table 3), seven genes (bus-8, cdk-4, cki-1, kin-10, mlt-11, nhr-23, and K10D6.2) showed defects in seam syncytium and alae formation (Table 4, Table 5), and three genes (lin-1, kin-10, and pak-1) had defects in L4 vulva formation (Table 6). "
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    ABSTRACT: The evolutionarily conserved Wnt/β-catenin signaling pathway plays a fundamental role during metazoan development, regulating numerous processes including cell fate specification, cell migration, and stem cell renewal. Wnt ligand binding leads to stabilization of the transcriptional effector β-catenin and upregulation of target gene expression to mediate a cellular response. During larval development of the nematode Caenorhabditis elegans, Wnt/β-catenin pathways act in fate specification of two hypodermal cell types, the ventral vulval precursor cells (VPCs) and the lateral seam cells. As little is known about targets of the Wnt signaling pathways acting during larval VPC and seam cell differentiation, we sought to identify genes regulated by Wnt signaling in these two hypodermal cell types. We conditionally activated Wnt signaling in larva animals and performed cell type-specific 'mRNA tagging' to enrich for VPC and seam cell specific mRNAs, then used microarray analysis to examine gene expression compared to control animals. 239 genes activated in responsive to Wnt signaling were identified, and we characterized 50 genes further. The majority of these genes are expressed in seam and or vulval lineages during normal development, and reduction of function for nine genes caused defects in the proper division, fate specification, fate execution or differentiation of seam cells and vulval cells. Therefore, the combination of these techniques was successful at identifying potential cell type specific Wnt pathway target genes from a small number of cells and increasing our knowledge of the specification and behavior of these C. elegans larval hypodermal cells. Copyright © 2015 Author et al.
    G3-Genes Genomes Genetics 06/2015; DOI:10.1534/g3.115.017715 · 2.51 Impact Factor
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    • "BAR-1 is regulated by the axin-like protein PRY-1, the GSK3β homolog SGG-1 and the APC-like protein APR-11718. Among the processes influenced by BAR-1 are P12 cell fate specification1419 and mab-5 expression in the neuroblast QL1520. Moreover, BAR-1 is involved in vulval precursor cell specification in the early L1 stage of C. elegans through transcriptional activation of the Hox gene lin-39. "
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    ABSTRACT: C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling components are known. Four β-catenins are important gene expression regulators in Wnt-signalling. One of these, bar-1, is part of the canonical Wnt-pathway. Together with Wnt effector pop-1, bar-1 forms a transcription activation complex which regulates the transcription of downstream genes. The effects of bar-1 loss-of-function mutations on many phenotypes have been studied well. However, the effects on global gene expression are unknown. Here we report the effects of a loss-of-function mutation bar-1(ga80). By analysing the transcriptome and developmental phenotyping we show that bar-1(ga80) impairs developmental timing. This developmental difference confounds the comparison of the gene expression profile between the mutant and the reference strain. When corrected for this difference it was possible to identify genes that were directly affected by the bar-1 mutation. We show that the Wnt-pathway itself is activated, as well as transcription factors elt-3, pqm-1, mdl-1 and pha-4 and their associated genes. The outcomes imply that this response compensates for the loss of functional bar-1. Altogether we show that bar-1 loss-of function leads to delayed development possibly caused by an induction of a stress response, reflected by daf-16 activated genes.
    Scientific Reports 05/2014; 4:4926. DOI:10.1038/srep04926 · 5.58 Impact Factor
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    • "These 22 cells undergo cell migration and fusion events to eventually form the adult vulval structure (reviewed in [25]). In Pvl mutants a single protrusion is formed, which is caused by eversion of the vulval tissue [56]. "
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