Genetic regulation of entry into meiosis in Caenorhabditis elegans

The Caenorhabditis elegans germline is composed of mitotically dividing cells at the distal end that give rise to meiotic cells more proximally. Specification of the distal region as mitotic relies on induction by the somatic distal tip cell and the glp-1 signal transduction pathway. However, the genetic control over the transition from mitosis to meiosis is not understood. In this paper, we report the identification of a gene, gld-2, that has at least two functions in germline development. First, gld-2 is required for normal progression through meiotic prophase. Second, gld-2 promotes entry into meiosis from the mitotic cell cycle. With respect to this second function, gld-2 appears to be functionally redundant with a previously described gene, gld-1 (Francis, R., Barton, M. K., Kimble, J. and Schedl, T. (1995) Genetics 139, 579–606). Germ cells in gld-1(o) and gld-2 single mutants enter meiosis at the normal time, but germ cells in gld-2 gld-1(o) double mutants do not enter meiosis. Instead, the double mutant germline is mitotic throughout and forms a large tumor. We suggest that gld-1 and gld-2 define two independent regulatory pathways, each of which can be sufficient for entry into meiosis. Epistasis analyses show that gld-1 and gld-2 work downstream of the glp-1 signal transduction pathway. Therefore, we hypothesize that glp-1 promotes proliferation by inhibiting the meiosis-promoting functions of gld-1 and gld-2.

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The p38 signal transduction pathway participates in the oxidative stress-mediated translocation of DAF-16 to Caenorhabditis elegans nuclei

Mechanisms of Ageing and Development ◽

10.1016/j.mad.2004.11.012 ◽

2005 ◽

Vol 126 (6-7) ◽

pp. 642-647 ◽

Cited By ~ 44

Author(s):

Masaki Kondo ◽

Sumino Yanase ◽

Takamasa Ishii ◽

Philip S. Hartman ◽

Kunihiro Matsumoto ◽

...

Keyword(s):

Oxidative Stress ◽

Signal Transduction ◽

Caenorhabditis Elegans ◽

Signal Transduction Pathway ◽

Transduction Pathway

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A Ras-mediated signal transduction pathway is involved in the control of sex myoblast migration in Caenorhabditis elegans

Development ◽

10.1242/dev.122.9.2823 ◽

1996 ◽

Vol 122 (9) ◽

pp. 2823-2833 ◽

Cited By ~ 2

Author(s):

M. Sundaram ◽

J. Yochem ◽

M. Han

Keyword(s):

Signal Transduction ◽

Caenorhabditis Elegans ◽

Growth Factor Receptor ◽

Signal Transduction Pathway ◽

Body Region ◽

Transduction Pathway ◽

Loss Of Function ◽

Ras Pathway ◽

Mosaic Analysis ◽

Sex Myoblasts

Sex myoblast migration in the Caenorhabditis elegans hermaphrodite represents a simple, genetically amenable model system for studying how cell migration is regulated during development. Two separable components of sex myoblast guidance have been described: a gonad-independent mechanism sufficient for the initial anterior migration to the mid-body region, and a gonad-dependent mechanism required for precise final positioning (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041–1052). Here, we demonstrate a role for a Ras-mediated signal transduction pathway in controlling sex myoblast migration. Loss-of-function mutations in let-60 ras, ksr-1, lin-45 raf, let-537/mek-2 or sur-1/mpk-1 cause defects in sex myoblast final positions that resemble those seen in gonad-ablated animals, while constitutively active let-60 ras(G13E) trans-genes allow fairly precise positioning to occur in the absence of the gonad. A mosaic analysis demonstrated that let-60 ras is required within the sex myoblasts to control proper positioning. Our results suggest that gonadal signals normally stimulate let-60 ras activity in the sex myoblasts, thereby making them competent to sense or respond to positional cues that determine the precise endpoint of migration. let-60 ras may have additional roles in sex myoblast guidance as well. Finally, we have also investigated genetic interactions between let-60 ras and other genes important for sex myoblast migration, including egl-15, which encodes a fibroblast growth factor receptor tyrosine kinase (D. L. DeVore, H. R. Horvitz and M. J. Stern (1995) Cell 83, 611–623). Since mutations reducing Ras pathway activity cause a different phenotype than those reducing egl-15 activity and since constitutive Ras activity only partially suppresses the migration defects of egl-15 mutants, we argue that let-60 ras and egl-15 do not act together in a single linear pathway.

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Gain-of-Function Mutations in the Caenorhabditis elegans lin-1 ETS Gene Identify a C-Terminal Regulatory Domain Phosphorylated by ERK MAP Kinase

Genetics ◽

10.1093/genetics/149.4.1809 ◽

1998 ◽

Vol 149 (4) ◽

pp. 1809-1822 ◽

Cited By ~ 5

Author(s):

Dave Jacobs ◽

Greg J Beitel ◽

Scott G Clark ◽

H Robert Horvitz ◽

Kerry Kornfeld

Keyword(s):

Signal Transduction ◽

Caenorhabditis Elegans ◽

Tyrosine Kinase ◽

Map Kinase ◽

Cell Fate ◽

Receptor Tyrosine Kinase ◽

Signal Transduction Pathway ◽

Negative Regulation ◽

Transduction Pathway ◽

C Terminus

Abstract Genetic analysis of lin-1 loss-of-function mutations suggests that lin-1 controls multiple cell-fate decisions during Caenorhabditis elegans development and is negatively regulated by a conserved receptor tyrosine kinase-Ras-ERK mitogen-activated protein (MAP) kinase signal transduction pathway. LIN-1 protein contains an ETS domain and presumably regulates transcription. We identified and characterized six gain-of-function mutations that define a new class of lin-1 allele. These lin-1 alleles appeared to be constitutively active and unresponsive to negative regulation. Each allele has a single-base change that affects the predicted C terminus of LIN-1, suggesting this region is required for negative regulation. The C terminus of LIN-1 was a high-affinity substrate for Erk2 in vitro, suggesting that LIN-1 is directly regulated by ERK MAP kinase. Because mpk-1 ERK MAP kinase controls at least one cell-fate decision that does not require lin-1, our results suggest that MPK-1 contributes to the specificity of this receptor tyrosine kinase-Ras-MAP kinase signal transduction pathway by phosphorylating different proteins in different developmental contexts. These lin-1 mutations all affect a four-amino-acid motif, FQFP, that is conserved in vertebrate and Drosophila ETS proteins that are also phosphorylated by ERK MAP kinase. This sequence may be a substrate recognition motif for the ERK subfamily of MAP kinases.

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