Abstract
Experiments with mammalian tissue culture cells have implicated the small GTPase Ras in the control of cellular proliferation. Evidence is presented here that this is not the case for a living animal, the nematode Caenorhabditis elegans: proliferation late in embryogenesis and throughout the four larval stages is not noticeably affected in animals lacking Ras in various parts of their cell lineages. Instead, genetic mosaic analysis of the let-60 gene suggests that Ras is required only, at least later in development (a maternal effect cannot be excluded), for establishment of a few temporally and spatially distinct cell fates. Only one of these, the duct cell fate, appears to be essential for viability.
Full Text
The Full Text of this article is available as a PDF (263.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aroian R. V., Koga M., Mendel J. E., Ohshima Y., Sternberg P. W. The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily. Nature. 1990 Dec 20;348(6303):693–699. doi: 10.1038/348693a0. [DOI] [PubMed] [Google Scholar]
- Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
- Beitel G. J., Clark S. G., Horvitz H. R. Caenorhabditis elegans ras gene let-60 acts as a switch in the pathway of vulval induction. Nature. 1990 Dec 6;348(6301):503–509. doi: 10.1038/348503a0. [DOI] [PubMed] [Google Scholar]
- Chamberlin H. M., Sternberg P. W. The lin-3/let-23 pathway mediates inductive signalling during male spicule development in Caenorhabditis elegans. Development. 1994 Oct;120(10):2713–2721. doi: 10.1242/dev.120.10.2713. [DOI] [PubMed] [Google Scholar]
- Church D. L., Guan K. L., Lambie E. J. 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. Development. 1995 Aug;121(8):2525–2535. doi: 10.1242/dev.121.8.2525. [DOI] [PubMed] [Google Scholar]
- DeVore D. L., Horvitz H. R., Stern M. J. An FGF receptor signaling pathway is required for the normal cell migrations of the sex myoblasts in C. elegans hermaphrodites. Cell. 1995 Nov 17;83(4):611–620. doi: 10.1016/0092-8674(95)90101-9. [DOI] [PubMed] [Google Scholar]
- Durkin J. P., Whitfield J. F. The viral Ki-ras gene must be expressed in the G2 phase if ts Kirsten sarcoma virus-infected NRK cells are to proliferate in serum-free medium. Mol Cell Biol. 1987 Jan;7(1):444–449. doi: 10.1128/mcb.7.1.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Han M., Aroian R. V., Sternberg P. W. The let-60 locus controls the switch between vulval and nonvulval cell fates in Caenorhabditis elegans. Genetics. 1990 Dec;126(4):899–913. doi: 10.1093/genetics/126.4.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Han M., Sternberg P. W. let-60, a gene that specifies cell fates during C. elegans vulval induction, encodes a ras protein. Cell. 1990 Nov 30;63(5):921–931. doi: 10.1016/0092-8674(90)90495-z. [DOI] [PubMed] [Google Scholar]
- Hedgecock E. M., Herman R. K. The ncl-1 gene and genetic mosaics of Caenorhabditis elegans. Genetics. 1995 Nov;141(3):989–1006. doi: 10.1093/genetics/141.3.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herman M. A., Vassilieva L. L., Horvitz H. R., Shaw J. E., Herman R. K. The C. elegans gene lin-44, which controls the polarity of certain asymmetric cell divisions, encodes a Wnt protein and acts cell nonautonomously. Cell. 1995 Oct 6;83(1):101–110. doi: 10.1016/0092-8674(95)90238-4. [DOI] [PubMed] [Google Scholar]
- Hou X. S., Chou T. B., Melnick M. B., Perrimon N. The torso receptor tyrosine kinase can activate Raf in a Ras-independent pathway. Cell. 1995 Apr 7;81(1):63–71. doi: 10.1016/0092-8674(95)90371-2. [DOI] [PubMed] [Google Scholar]
- Kimble J., Hirsh D. The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans. Dev Biol. 1979 Jun;70(2):396–417. doi: 10.1016/0012-1606(79)90035-6. [DOI] [PubMed] [Google Scholar]
- Koga M., Ohshima Y. Mosaic analysis of the let-23 gene function in vulval induction of Caenorhabditis elegans. Development. 1995 Aug;121(8):2655–2666. doi: 10.1242/dev.121.8.2655. [DOI] [PubMed] [Google Scholar]
- Lackner M. R., Kornfeld K., Miller L. M., Horvitz H. R., Kim S. K. A MAP kinase homolog, mpk-1, is involved in ras-mediated induction of vulval cell fates in Caenorhabditis elegans. Genes Dev. 1994 Jan;8(2):160–173. doi: 10.1101/gad.8.2.160. [DOI] [PubMed] [Google Scholar]
- Maruta H., Burgess A. W. Regulation of the Ras signalling network. Bioessays. 1994 Jul;16(7):489–496. doi: 10.1002/bies.950160708. [DOI] [PubMed] [Google Scholar]
- Mello C. C., Kramer J. M., Stinchcomb D., Ambros V. Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 1991 Dec;10(12):3959–3970. doi: 10.1002/j.1460-2075.1991.tb04966.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller L. M., Waring D. A., Kim S. K. Mosaic analysis using a ncl-1 (+) extrachromosomal array reveals that lin-31 acts in the Pn.p cells during Caenorhabditis elegans vulval development. Genetics. 1996 Jul;143(3):1181–1191. doi: 10.1093/genetics/143.3.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mulcahy L. S., Smith M. R., Stacey D. W. Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells. Nature. 1985 Jan 17;313(5999):241–243. doi: 10.1038/313241a0. [DOI] [PubMed] [Google Scholar]
- Nelson F. K., Riddle D. L. Functional study of the Caenorhabditis elegans secretory-excretory system using laser microsurgery. J Exp Zool. 1984 Jul;231(1):45–56. doi: 10.1002/jez.1402310107. [DOI] [PubMed] [Google Scholar]
- Simske J. S., Kim S. K. Sequential signalling during Caenorhabditis elegans vulval induction. Nature. 1995 May 11;375(6527):142–146. doi: 10.1038/375142a0. [DOI] [PubMed] [Google Scholar]
- Sulston J. E., Horvitz H. R. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol. 1977 Mar;56(1):110–156. doi: 10.1016/0012-1606(77)90158-0. [DOI] [PubMed] [Google Scholar]
- Sulston J. E., Schierenberg E., White J. G., Thomson J. N. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol. 1983 Nov;100(1):64–119. doi: 10.1016/0012-1606(83)90201-4. [DOI] [PubMed] [Google Scholar]
- Sundaram M., Han M. Control and integration of cell signaling pathways during C. elegans vulval development. Bioessays. 1996 Jun;18(6):473–480. doi: 10.1002/bies.950180609. [DOI] [PubMed] [Google Scholar]
- Sundaram M., Yochem J., Han M. A Ras-mediated signal transduction pathway is involved in the control of sex myoblast migration in Caenorhabditis elegans. Development. 1996 Sep;122(9):2823–2833. doi: 10.1242/dev.122.9.2823. [DOI] [PubMed] [Google Scholar]