Cyclic GMP-dependent protein kinase EGL-4 controls body size and lifespan inC. elegans

Development (Cambridge) - Tập 130 Số 6 - Trang 1089-1099 - 2003
Takashi Hirose1, Yoshiya Nakano2, Yasuko Nagamatsu2, Takashi Misumi2, Hiromitsu Ohta2, Yasumi Ohshima2
1Present address: Research Institute of Microbial Diseases, Osaka University,Yamadaoka, Suita 565-0871, Japan
2Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Hakozaki, Fukuoka 812-8581, Japan

Tóm tắt

We designed an automatic system to measure body length, diameters and volume of a C. elegans worm. By using this system, mutants with an increased body volume exceeding 50% were isolated. Four of them are grossly normal in morphology and development, grow longer to be almost twice as big,and have weak egg-laying defects and extended lifespan. All the four mutants have a mutation in the egl-4 gene. We show that the egl-4gene encodes cGMP-dependent protein kinases. egl-4 promoter::gfp fusion genes are mainly expressed in head neurons, hypodermis, intestine and body wall muscles. Procedures to analyze morphology and volume of major organs were developed. The results indicate that volumes of intestine, hypodermis and muscle and cell volumes in intestine and muscle are increased in theegl-4 mutants, whereas cell numbers are not. Experiments on genetic interaction suggest that the cGMP-EGL-4 signaling pathway represses body size and lifespan through DBL-1/TGF-β and insulin pathways, respectively.

Từ khóa


Tài liệu tham khảo

Böhni, R., Riesgo-Escovar, J., Oldham, S., Brogiolo, W.,Stocker, H., Andruss, B. F., Beckingham, K. and Hafen, E.(1999). Autonomous control of cell and organ size by CHICO, aDrosophila homolog of vertebrate IRS1-4. Cell97,865-875.

Brenner, S. (1974). The genetics ofCaenorhabditis elegans.Genetics77, 71-94.

Brock, D. A. and Gomer, R. H. (1999). A cell-counting factor regulating structure size in Dictyostelium.Genes Dev.13,1960-1969.

Brodsky, V. Y. and Uryvaeva, I. V. (1985).Genome Multiplication in Growth and Development. Cambridge: Cambridge University Press.

Conlon, I. and Raff, M. (1999). Size control in animal development. Cell96,235-244.

Cossins, A. R. (1991). A sense of cell size.Nature352,667-668.

Crackower, M. A., Scherrer, S. W., Rommens, J. M. and Hui, C. C. et al. (1996). Characterization of the split hand/split foot malformation locus SHFM1 at 7q21.3-q22.1 and analysis of a candidate gene for its expression during limb development. Hum. Mol. Genet.5,571-579.

Daniels, S. A., Ailion, M., Thomas, J. H. and Sengupta, P.(2000). egl-4 acts through a transforming growth factor-β/SMAD pathway in Caenorhabditis elegans to regulate multiple neuronal circuits in response to sensory cues.Genetics156,123-141.

del Castillo, J. and Morales, T. (1967). The electrical and mechanical activity of the esophageal cell of Ascaris lumbricoides.J. Gen. Physiol.50,603-629.

Estevez, M., Attisano, L., Wrana, J. L., Albert, P. S.,Massague, J. and Riddle, D. L. (1993). The daf-4gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development. Nature365,644-649.

Fire, A., Harrison, S. W. and Dixon, D. (1990). A modular set of lacZ fusion vectors for studying gene expression inCaenorhabditis elegans.Gene93,189-198.

Flemming, A. J., Shen, Z.-Z., Cunha, A., Emmons, S. W. and Leroi, A. M. (2000). Somatic polyploidization and cellular proliferation drive body size evolution in nematodes. Proc. Natl. Acad. Sci. USA97,5285-5290.

Francis, R., Barton, M. K., Kimble, J. and Schedl, T.(1995). gld-1, a tumor suppressor gene required for oocyte development in Caenorhabditis elegans.Genetics139,579-606.

Fujiwara, M., Sengupta, P. and McIntire, S. L.(2002). Regulation of body size and behavioral state of C. elegans by sensory perception and EGL-4 cGMP-dependent protein kinase.Neuron36,1091-1102.

Gudi, T., Lohmann, S. M. and Pilz, R. B.(1997). Regulation of gene expression by cyclic GMP-dependent protein kinase requires nuclear translocation of the kinase: identification of a nuclear localization signal. Mol. Cell. Biol.17,5244-5254.

Henery, C. C., Bard, J. B. L. and Kaufman, M. H.(1992). Tetraploidy in mice, embryonic cell number, and the grain of the developmental map. Dev. Biol.152,233-241.

Hsin, H. and Kenyon, C. (1999). Signals from the reproductive system regulate the lifespan of C. elegans.Nature399,362-366.

Kenyon, C., Chang, J., Gensch, E., Rudner, A. and Tabtiang,R. (1993). A C. elegans mutant that lives twice as long as wild type. Nature366,461-464.

Koga, M., Take-uchi, M., Tameishi, T. and Ohshima, Y.(1999). Control of DAF-7 TGF-β expression and neuronal process development by a receptor tyrosine kinase KIN-8 in Caenorhabdidits elegans.Development126,5387-5398.

Krishna, S., Maduzia, L. L. and Padgett, R. W.(1999). Specificity of TGFβ-signaling is conferred by distinct type I receptors and their associated SMAD proteins inCaenorhabditis elegans.Development126,251-260.

Leevers, S. J., Weinkove, D., MacDougall, L. K., Hafen, E. and Waterfield, M. D. (1996). The Drosophilaphosphoinositide 3-kinase Dp110 promotes cell growth. EMBO J.15,6584-6594.

L'Etoile, N., Coburn, C., Kistler, A., Gallegos, G. and Bargmann, C. (2002). The cyclic GMP-dependent protein kinase EGL-4 directs olfactory adaptation in C. elegans.Neuron36,1079-1089.

Li, S., Crenshaw, E. B. III, Rawson, E. J., Simmons, D. M.,Swanson, L. W. and Rosenfeld, M. G. (1990). Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1.Nature347,528-533.

Liu, Z., Kirch, S. and Ambros, V. (1995). TheCaenorhabditis elegans heterochronic gene pathway controls stage-specific transcription of collagen genes.Development121,2471-2478.

Lohmann, S. M., Vaandrager, A. B., Smolenski, A., Walter, U. and de Jonge, H. R. (1997). Distinct and specific functions of cGMP-dependent protein kinases. Trends Biochem. Sci.22,307-312.

McPherron, A. C., Lawler, A. M. and Lee, S. J.(1997). Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature387, 83-90.

Mello, C. C., Kramer, J. M., Stinchcomb, D. and Ambros, V.(1991). Efficient gene transfer in C. elegans:extrachromosomal maintenance and integration of transforming sequences.EMBO J.12,3959-3970.

Morita, K., Chow, K. L. and Ueno, N. (1999). Regulation of body length and male tail ray pattern formation ofCaenorhabditis elegans by a member of TGFβ family.Development126,1337-1347.

Nakayama, K., Ishida, N., Shirane, M., Inomata, A., Inoue, T.,Shishido, N., Horii, I., Loh, D. Y. and Nakayama, K. (1996). Mice lacking p27Kip1 display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors.Cell85,707-720.

Ogg, S., Paradis, S., Gottlieb, S., Patterson, G. I., Lee, L.,Tissenbaum, H. A. and Ruvkun, G. (1997). The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans.Nature389,994-999.

Okkema, P. G., Harrison, S. W., Plunger, V., Aryana, A. and Fire, A. (1993). Sequence requirements for myosin gene expression and regulation in Caenorhabditis elegans.Genetics135,385-404.

Palmiter, R. D., Brinster, R. L., Hammer, R. E., Trumbauer, M. E., Rosenfeld, M. G., Birnberg, N. C. and Evans, R. M.(1982). Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes.Nature300,611-615.

Paradis, S., Ailion, M., Toker, A., Thomas, J. H. and Ruvkun,G. (1999). A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause inCaenorhabditis elegans.Genes Dev.13,1438-1452.

Patel, M. N., Knight, C. G., Karageorgi, C. and Leroi, A. M.(2002). Evolution of germ-line signals that regulate growth and aging in nematodes. Proc. Natl. Acad. Sci. USA99,769-774.

Patterson, G. I. and Padgett, R. W. (2000). TGFβ-related pathways. Roles in Caenorhabditis elegans development.Trends Genet.16,27-33.

Pfeifer, A., Aszodi, A., Seidler, U., Ruth, P., Hofmann, F. and Fässler, R. (1996). Intestinal secretory defects and dwarfism in mice lacking cGMP-dependent protein kinase II.Science274,2082-2086.

Pfeifer, A., Klatt, P., Massberg, S., Ny, L., Sausbier, M. and Hirnei, C. et al. (1998). Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J.17,3045-3051.

Randall, D., Burggren, W. and French, K.(1997). Animal Physiology. Mechanisms and Adaptation. 4th ed. New York: W. H. Freeman and Company.

Riddle, D. L. and Albert, P. S. (1997).Genetic and environmental regulation of dauer larva development. In C. elegans II (ed. D. L. Riddle et al.), pp.739-768. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Sambrook, J., Frisch, E. F. and Maniatis, T.(1989). Molecular Cloning. A Laboratory Manual, 2nd ed. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

Savage, C., Das, P., Finelli, A. L., Townsend, S. R., Sun,C.-Y., Baird, S. E. and Padgett, R. W. (1996).Caenorhabditis elegans genes sma-2, sma-3 and sma-4define a conserved family of transforming growth factor β pathway components. Proc. Natl. Acad. Sci. USA93,790-794.

Stansberry, J., Baude, E. J., Taylor, M. K., Chen, P., Jin,S.-W., Ellis, R. E. and Uhler, M. D. (2001). A cGMP-dependent protein kinase is implicated in wild-type motility in C. elegans.J. Neurochem.76,1177-1187.

Sulston, J. and Hodgkin, J. (1988). Methods. InThe Nematode Caenorhabditis elegans (ed. W. B. Wood),pp. 587-606. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.

Suzuki, Y., Yandell, M. D., Roy, P. J., Krishna, S.,Savage-Dunn, C., Ross, R. M., Padgett, R. W. and Wood, W. B.(1999). A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans.Development126,241-250.

Trent, C., Tsung, N. and Horvitz, H. R. (1983). Egg-laying defective mutants of the nematode Caenorhabditis elegans.Genetics104,619-647.

Waterston, R. H., Thomson, J. N. and Brenner, S.(1980). Mutants with altered muscle structure inCaenorhabditis elegans.Dev. Biol.77,271-302.

Wicks, S. R., Yeh, R. T., Gish, W. R., Waterston, R. H. and Plasterk, R. H. (2001). Rapid mapping in Caenorhabditis elegans using a high density polymorphism map. Nat. Genet.28,160-164.

Williams, B. D., Schrank, B., Huynh, C., Shownkeen, R. and Waterston, R. H. (1992). A genetic mapping system inCaenorhabditis elegans based on polymorphic sequence-tagged sites.Genetics131,609-624.

Thông tin
Thông tin xuất bản

Development (Cambridge)

Tập 130 Số 6

1089-1099

Thông tin tác giả