Three genes of the MAP kinase cascade, mek-2, mpk-1/sur-1 and let-60 ras, are required for meiotic cell cycle progression in Caenorhabditis elegans.

In the germline of Caenorhabditis elegans hermaphrodites, meiotic cell cycle progression occurs in spatially restricted regions. Immediately after leaving the distal mitotic region, germ cells enter meiosis and thereafter remain in the pachytene stage of first meiotic prophase for an extended period. At the dorsoventral gonadal flexure, germ cells exit pachytene and subsequently become arrested in diakinesis. We have found that exit from pachytene is dependent on the function of three members of the MAP kinase signaling cascade. One of these genes, mek-2, is a newly identified C. elegans MEK (MAP kinase kinase). The other two genes, mpk-1/sur-1 (MAP kinase) and let-60 ras, were previously identified based on their roles in vulval induction and are shown here to act in combination with mek-2 to permit exit from pachytene. Through genetic mosaic analysis, we demonstrate that the expression of mpk-1/sur-1 is required within the germline to permit exit from pachytene.

[1]  E. Krebs,et al.  Overexpression of mitogen-activated protein kinase kinase (MAPKK) and its mutants in NIH 3T3 cells. Evidence that MAPKK involvement in cellular proliferation is regulated by phosphorylation of serine residues in its kinase subdomains VII and VIII. , 1994, The Journal of biological chemistry.

[2]  M. Barton,et al.  fog-1, a regulatory gene required for specification of spermatogenesis in the germ line of Caenorhabditis elegans. , 1990, Genetics.

[3]  Steven N. Hird,et al.  Targeted mutations in the Caenorhabditis elegans POU homeo box gene ceh-18 cause defects in oocyte cell cycle arrest, gonad migration, and epidermal differentiation. , 1994, Genes & development.

[4]  C. Zheng,et al.  Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues. , 1994, The EMBO journal.

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

[6]  J. Parsons,et al.  Amino acid alterations within a highly conserved region of the Rous sarcoma virus src gene product pp60src inactivate tyrosine protein kinase activity , 1984, Molecular and cellular biology.

[7]  K. Guan,et al.  Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases. , 1993, The Journal of biological chemistry.

[8]  D. Baillie,et al.  Mutagenesis in Caenorhabditis elegans. II. A spectrum of mutational events induced with 1500 r of gamma-radiation. , 1985, Genetics.

[9]  R. Davis,et al.  The mitogen-activated protein kinase signal transduction pathway. , 1993, The Journal of biological chemistry.

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

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

[12]  J. Blenis,et al.  Signal transduction via the MAP kinases: proceed at your own RSK. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Jonathan A. Cooper.  MAP Kinase Pathways: Straight and narrow or tortuous and intersecting? , 1994, Current Biology.

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

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

[16]  P. Sternberg.  Intercellular signaling and signal transduction in C. elegans. , 1993, Annual review of genetics.

[17]  T. Hunter,et al.  The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. , 1988, Science.

[18]  C. Kenyon,et al.  The nematode Caenorhabditis elegans. , 1988, Science.

[19]  J Kimble,et al.  Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions. , 1991, Development.

[20]  R. K. Herman.  Crossover suppressors and balanced recessive lethals in Caenorhabditis elegans. , 1978, Genetics.

[21]  R. Ellis,et al.  The fog-3 gene and regulation of cell fate in the germ line of Caenorhabditis elegans. , 1995, Genetics.

[22]  A. Ullrich,et al.  Human proto‐oncogene c‐kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. , 1987, The EMBO journal.

[23]  M. Cobb,et al.  MAP kinase becomes stably activated at metaphase and is associated with microtubule-organizing centers during meiotic maturation of mouse oocytes. , 1993, Developmental biology.

[24]  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.

[25]  Paul W. Sternberg,et al.  C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation , 1993, Nature.

[26]  P. Sternberg,et al.  The let-60 locus controls the switch between vulval and nonvulval cell fates in Caenorhabditis elegans. , 1990, Genetics.

[27]  Susan S. Taylor,et al.  A template for the protein kinase family. , 1993, Trends in biochemical sciences.

[28]  S. Nishikawa,et al.  Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function. , 1991, Development.

[29]  G. Johnson,et al.  Sequential protein kinase reactions controlling cell growth and differentiation. , 1994, Current opinion in cell biology.

[30]  H. Horvitz,et al.  The Caenorhabditis elegans gene mek-2 is required for vulval induction and encodes a protein similar to the protein kinase MEK. , 1995, Genes & development.

[31]  S. Moody,et al.  Oculomotor neuroblast migration in the chick embryo in the absence of tecto-tegmental fibers. , 1979, Developmental biology.

[32]  P W Sternberg,et al.  Cell fate patterning during C. elegans vulval development. , 1993, Development (Cambridge, England). Supplement.

[33]  T. Schedl,et al.  Cell-cell interactions prevent a potential inductive interaction between soma and germline in C. elegans , 1990, Cell.

[34]  Min Han,et al.  MEK-2, a Caenorhabditis elegans MAP kinase kinase, functions in Ras-mediated vulval induction and other developmental events. , 1995, Genes & development.

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

[36]  H. Horvitz,et al.  The lin-12 locus specifies cell fates in caenorhabditis elegans , 1983, Cell.

[37]  F. Ruddle,et al.  Primary structure of c‐kit: relationship with the CSF‐1/PDGF receptor kinase family–oncogenic activation of v‐kit involves deletion of extracellular domain and C terminus. , 1988, The EMBO journal.

[38]  N. Perrimon,et al.  Control of cell fate determination by p21ras/Ras1, an essential component of torso signaling in Drosophila. , 1993, Genes & development.

[39]  F. James Rohlf,et al.  Biometry: The Principles and Practice of Statistics in Biological Research , 1969 .

[40]  J. Kimble,et al.  glp-1 Is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans , 1987, Cell.

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

[42]  T. Schedl.  The role of cell-cell interactions in postembryonic development of the Caenorhabditis elegans germ line. , 1991, Current opinion in genetics & development.

[43]  D. Moerman,et al.  Formaldehyde mutagenesis in the nematode Caenorhabditis elegans. , 1981, Mutation research.

[44]  E. Russell.  Hereditary anemias of the mouse: a review for geneticists. , 1979, Advances in genetics.

[45]  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.

[46]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[47]  P. Sternberg,et al.  Multiple functions of let-23, a Caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction. , 1991, Genetics.

[48]  P. Cohen,et al.  Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases , 1991, Nature.

[49]  R. K. Herman.  MOSAIC ANALYSIS IN THE NEMATODE CAENORHABDITIS ELEGANS , 2007, Journal of neurogenetics.

[50]  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.

[51]  P. Sternberg,et al.  Role of a raf proto-oncogene during Caenorhabditis elegans vulval development. , 1993, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[52]  E. Nishida,et al.  The MAP kinase cascade is essential for diverse signal transduction pathways. , 1993, Trends in biochemical sciences.

[53]  Jonathan A. Cooper,et al.  Requirements for phosphorylation of MAP kinase during meiosis in Xenopus oocytes. , 1992, Science.

[54]  M. Klass,et al.  Development of the male reproductive system and sexual transformation in the nematode Caenorhabditis elegans. , 1976, Developmental biology.

[55]  S. Nishikawa,et al.  The expression of c-kit protein during oogenesis and early embryonic development. , 1991, Biology of Reproduction.

[56]  C. Kenyon.  A gene involved in the development of the posterior body region of C. elegans , 1986, Cell.

[57]  E. Lambie,et al.  Genetic control of cell interactions in nematode development. , 1991, Annual review of genetics.

[58]  K. Manova,et al.  Gonadal expression of c-kit encoded at the W locus of the mouse. , 1990, Development.

[59]  J Kimble,et al.  lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans. , 1994, Development.

[60]  C. Crews,et al.  Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[61]  M. Klass,et al.  Development of the reproductive system of Caenorhabditis elegans. , 1976, Developmental biology.

[62]  D. Baillie,et al.  Mutagenesis in Caenorhabditis elegans: I. A rapid eukaryotic mutagen test system using the reciprocal translocation, eTI(III;V) , 1983 .

[63]  Paul W. Sternberg,et al.  Multiple intercellular signalling systems control the development of the Caenorhabditis elegans vulva , 1991, Nature.

[64]  S. Ward,et al.  Fertilization and sperm competition in the nematode Caenorhabditis elegans. , 1979, Developmental biology.