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Development 130 (6): 1089-1099

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

Takashi Hirose*,{dagger}, Yoshiya Nakano{dagger}, Yasuko Nagamatsu, Takashi Misumi, Hiromitsu Ohta, and Yasumi Ohshima{ddagger}

Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Hakozaki, Fukuoka 812-8581, Japan
* Present address: Research Institute of Microbial Diseases, Osaka University, Yamadaoka, Suita 565-0871, Japan

{ddagger} Author for correspondence (e-mail: yohshscb{at}

Accepted for publication 6 December 2002.

Abstract: 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-4 gene 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 the egl-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-ß and insulin pathways, respectively.

Key Words: cGMP-dependent protein kinase • Body size • Lifespan • C. elegans • EGL-4 • Big mutant

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