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

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.

[1]  S. K. Kim,et al.  The Caenorhabditis elegans APC-related gene apr-1 is required for epithelial cell migration and Hox gene expression. , 2000, Genes & development.

[2]  I. Chin-Sang,et al.  The Ephrin VAB-2/EFN-1 Functions in Neuronal Signaling to Regulate Epidermal Morphogenesis in C. elegans , 1999, Cell.

[3]  T. Pawson,et al.  Multiple ephrins control cell organization in C. elegans using kinase-dependent and -independent functions of the VAB-1 Eph receptor. , 1999, Molecular cell.

[4]  R. Blelloch,et al.  Control of cell migration during Caenorhabditis elegans development. , 1999, Current opinion in cell biology.

[5]  M. Meneghini,et al.  Wnt pathway components orient a mitotic spindle in the early Caenorhabditis elegans embryo without requiring gene transcription in the responding cell. , 1999, Genes & development.

[6]  N. Perrimon,et al.  Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling , 1999, Nature.

[7]  H. Horvitz,et al.  UNC-84 localizes to the nuclear envelope and is required for nuclear migration and anchoring during C. elegans development. , 1999, Development.

[8]  K. Nishiwaki Mutations affecting symmetrical migration of distal tip cells in Caenorhabditis elegans. , 1999, Genetics.

[9]  M. Labouesse,et al.  lir-2, lir-1 and lin-26 encode a new class of zinc-finger proteins and are organized in two overlapping operons both in Caenorhabditis elegans and in Caenorhabditis briggsae. , 1999, Genetics.

[10]  J. White,et al.  Formation of the vulva in Caenorhabditis elegans: a paradigm for organogenesis. , 1999, Development.

[11]  H. Horvitz,et al.  sqv mutants of Caenorhabditis elegans are defective in vulval epithelial invagination. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  H. Horvitz,et al.  Three proteins involved in Caenorhabditis elegans vulval invagination are similar to components of a glycosylation pathway. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Whangbo,et al.  A Wnt signaling pathway controls hox gene expression and neuroblast migration in C. elegans. , 1999, Development.

[14]  M. Han,et al.  COG-2, a sox domain protein necessary for establishing a functional vulval-uterine connection in Caenorhabditis elegans. , 1999, Development.

[15]  Stuart K. Kim,et al.  The beta-catenin homolog BAR-1 and LET-60 Ras coordinately regulate the Hox gene lin-39 during Caenorhabditis elegans vulval development. , 1998, Development.

[16]  H. Horvitz,et al.  Gain-of-function mutations in the Caenorhabditis elegans lin-1 ETS gene identify a C-terminal regulatory domain phosphorylated by ERK MAP kinase. , 1998, Genetics.

[17]  P. Sternberg,et al.  Interactions of EGF, Wnt and HOM-C genes specify the P12 neuroectoblast fate in C. elegans. , 1998, Development.

[18]  Stuart K. Kim,et al.  MAP Kinase Signaling Specificity Mediated by the LIN-1 Ets/LIN-31 WH Transcription Factor Complex during C. elegans Vulval Induction , 1998, Cell.

[19]  A. Chisholm,et al.  The VAB-1 Eph Receptor Tyrosine Kinase Functions in Neural and Epithelial Morphogenesis in C. elegans , 1998, Cell.

[20]  C. Kenyon,et al.  The Hox gene lin-39 is required during C. elegans vulval induction to select the outcome of Ras signaling. , 1998, Development.

[21]  D. Riddle C. Elegans II , 1998 .

[22]  P. Sternberg,et al.  The PAX gene egl-38 mediates developmental patterning in Caenorhabditis elegans. , 1997, Development.

[23]  R. Moon,et al.  A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. , 1997, Genes & development.

[24]  N. Perrimon,et al.  The Drosophila sugarless gene modulates Wingless signaling and encodes an enzyme involved in polysaccharide biosynthesis. , 1997, Development.

[25]  Bruce Bowerman,et al.  Wnt Signaling Polarizes an Early C. elegans Blastomere to Distinguish Endoderm from Mesoderm , 1997, Cell.

[26]  C. Mello,et al.  Wnt Signaling and an APC-Related Gene Specify Endoderm in Early C. elegans Embryos , 1997, Cell.

[27]  J. Marsh,et al.  Defects in glucuronate biosynthesis disrupt Wingless signaling in Drosophila. , 1997, Development.

[28]  W. A. Johnson,et al.  Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling. , 1997, Development.

[29]  S. K. Kim,et al.  Mechanism of activation of the Caenorhabditis elegans ras homologue let-60 by a novel, temperature-sensitive, gain-of-function mutation. , 1997, Genetics.

[30]  Mariann Bienz,et al.  LEF-1, a Nuclear Factor Coordinating Signaling Inputs from wingless and decapentaplegic , 1997, Cell.

[31]  K. Kornfeld,et al.  Vulval development in Caenorhabditis elegans. , 1997, Trends in genetics : TIG.

[32]  P. Sternberg,et al.  Caenorhabditis elegans HOM-C genes regulate the response of vulval precursor cells to inductive signal. , 1997, Developmental biology.

[33]  Iva Greenwald,et al.  Development of the Vulva , 1997 .

[34]  D. Riddle,et al.  Male Development and Mating Behavior -- C. elegans II , 1997 .

[35]  D. Riddle,et al.  Cell and Growth Cone Migrations -- C. elegans II , 1997 .

[36]  D. Riddle,et al.  Development of the Vulva -- C. elegans II , 1997 .

[37]  N. Perrimon,et al.  The segment polarity gene porcupine encodes a putative multitransmembrane protein involved in Wingless processing. , 1996, Genes & development.

[38]  J. Culotti,et al.  UNC-40, a C. elegans Homolog of DCC (Deleted in Colorectal Cancer), Is Required in Motile Cells Responding to UNC-6 Netrin Cues , 1996, Cell.

[39]  R. Moon,et al.  Signal transduction through beta-catenin and specification of cell fate during embryogenesis. , 1996, Genes & development.

[40]  L. Honigberg,et al.  Neuronal cell migration in C. elegans: regulation of Hox gene expression and cell position. , 1996, Development.

[41]  P. Sternberg,et al.  Coordinated morphogenesis of epithelia during development of the Caenorhabditis elegans uterine-vulval connection. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[42]  H. Horvitz,et al.  The Caenorhabditis elegans gene lin-17, which is required for certain asymmetric cell divisions, encodes a putative seven-transmembrane protein similar to the Drosophila frizzled protein. , 1996, Genes & development.

[43]  M. Basson,et al.  The Caenorhabditis elegans gene sem-4 controls neuronal and mesodermal cell development and encodes a zinc finger protein. , 1996, Genes & development.

[44]  J. Bettinger,et al.  Stage-specific accumulation of the terminal differentiation factor LIN-29 during Caenorhabditis elegans development. , 1996, Development.

[45]  H. Horvitz,et al.  The Caenorhabditis elegans gene lin-1 encodes an ETS-domain protein and defines a branch of the vulval induction pathway. , 1995, Genes & development.

[46]  H. Horvitz,et al.  The C. elegans gene lin-44, which controls the polarity of certain asymmetric cell divisions, encodes a Wnt protein and acts cell nonautonomously , 1995, Cell.

[47]  B. Gumbiner Signal transduction of beta-catenin. , 1995, Current opinion in cell biology.

[48]  H. Horvitz,et al.  Patterning of the Caenorhabditis elegans head region by the Pax-6 family member vab-3 , 1995, Nature.

[49]  Y. Ohshima,et al.  Mosaic analysis of the let-23 gene function in vulval induction of Caenorhabditis elegans. , 1995, Development.

[50]  Seung K. Kim,et al.  Sequential signalling during Caenorhabditis elegans vulval induction , 1995 .

[51]  I. Greenwald,et al.  lin-25, a gene required for vulval induction in Caenorhabditis elegans. , 1995, Genes & development.

[52]  H. Horvitz,et al.  The Caenorhabditis elegans gene lin-26 is required to specify the fates of hypodermal cells and encodes a presumptive zinc-finger transcription factor. , 1994, Development.

[53]  S. K. Kim,et al.  Signal transduction and cell fate specification during Caenorhabditis elegans vulval development. , 1994, Current opinion in genetics & development.

[54]  H. Horvitz,et al.  The Caenorhabditis elegans gene lin-44 controls the polarity of asymmetric cell divisions. , 1994, Development.

[55]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[56]  H. Horvitz,et al.  A MAP kinase homolog, mpk-1, is involved in ras-mediated induction of vulval cell fates in Caenorhabditis elegans. , 1994, Genes & development.

[57]  Min Han,et al.  Suppression of activated Let-60 ras protein defines a role of Caenorhabditis elegans Sur-1 MAP kinase in vulval differentiation. , 1994, Genes & development.

[58]  N. Perrimon,et al.  Mutations in the segment polarity genes wingless and porcupine impair secretion of the wingless protein. , 1993, The EMBO journal.

[59]  Andrew D. Chisholm,et al.  Control of cell fates in the central body region of C. elegans by the homeobox gene lin-39 , 1993, Cell.

[60]  C. Kenyon,et al.  A homeotic gene cluster patterns the anteroposterior body axis of C. elegans , 1993, Cell.

[61]  S. K. Kim,et al.  lin-31, a Caenorhabditis elegans HNF-3/fork head transcription factor homolog, specifies three alternative cell fates in vulval development. , 1993, Genes & development.

[62]  G. Seydoux,et al.  Isolation and characterization of mutations causing abnormal eversion of the vulva in Caenorhabditis elegans. , 1993, Developmental biology.

[63]  C. Huynh,et al.  A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites. , 1992, Genetics.

[64]  A. Chisholm,et al.  Control of cell fate in the tail region of C. elegans by the gene egl-5. , 1991, Development.

[65]  Paul W. Sternberg,et al.  The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily , 1990, Nature.

[66]  H. Horvitz,et al.  Caenorhabditis elegans ras gene let-60 acts as a switch in the pathway of vulval induction , 1990, Nature.

[67]  P. Sternberg,et al.  let-60, a gene that specifies cell fates during C. elegans vulval induction, encodes a ras protein , 1990, Cell.

[68]  E. Hedgecock,et al.  Limitation of the size of the vulval primordium of Caenorhabditis elegans by lin-15 expression in surrounding hypodermis , 1990, Nature.

[69]  H. Horvitz,et al.  Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-II , 1990, Nature.

[70]  Paul W. Sternberg,et al.  The combined action of two intercellular signaling pathways specifies three cell fates during vulval induction in C. elegans , 1989, Cell.

[71]  N. Munakata [Genetics of Caenorhabditis elegans]. , 1989, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[72]  H. Horvitz,et al.  A genetic pathway for the development of the Caenorhabditis elegans HSN motor neurons , 1988, Nature.

[73]  H. Horvitz,et al.  lin-17 mutations of Caenorhabditis elegans disrupt certain asymmetric cell divisions. , 1988, Developmental biology.

[74]  Paul W. Sternberg,et al.  Lateral inhibition during vulval induction in Caenorhabditis elegans , 1988, Nature.

[75]  Kathleen Weston,et al.  The Caenorhabditis elegans lin-12 gene encodes a transmembrane protein with overall similarity to Drosophila Notch , 1988, Nature.

[76]  H. Horvitz,et al.  A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans , 1987, Nature.

[77]  Paul W. Sternberg,et al.  Pattern formation during vulval development in C. elegans , 1986, Cell.

[78]  H. Horvitz,et al.  Identification and characterization of 22 genes that affect the vulval cell lineages of the nematode Caenorhabditis elegans. , 1985, Genetics.

[79]  P. Sternberg,et al.  Genes that affect cell fates during the development of Caenorhabditis elegans. , 1985, Cold Spring Harbor symposia on quantitative biology.

[80]  H. Horvitz,et al.  Egg-laying defective mutants of the nematode Caenorhabditis elegans. , 1983, Genetics.

[81]  J E Sulston,et al.  Abnormal cell lineages in mutants of the nematode Caenorhabditis elegans. , 1981, Developmental biology.

[82]  J. Sulston,et al.  Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans. , 1980, Genetics.

[83]  J. Sulston,et al.  Regulation and cell autonomy during postembryonic development of Caenorhabditis elegans. , 1980, Developmental biology.

[84]  J. Sulston,et al.  Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. , 1977, Developmental biology.

[85]  S. Brenner The genetics of Caenorhabditis elegans. , 1974, Genetics.