cGMP and a germ-line signal control body size in C. elegans through cGMP-dependent protein kinase EGL-4

Mechanisms involved in the control of body size are largely unknown. In the nematode C. elegans, several small body size mutants were isolated, and the responsible genes were reported to encode putative components of a TGFbeta signalling pathway. Recently, mutants in the egl-4 gene encoding cGMP-dependent protein kinases were found to have a larger body size, and it was suggested that EGL-4 down-regulates the TGFbeta/DBL-1 pathway. We show that a permeable cGMP analogue 8-Br-cGMP significantly reduces body size of the wild-type but not that of an egl-4 mutant, indicating that cGMP controls body size through EGL-4. Laser ablation of germ-line cells revealed that a germ-line signal and EGL-4 function in the same pathway. Targeted expression of EGL-4 indicates that EGL-4 can function in hypodermis, neurones and intestine both cell-autonomously and cell-nonautonomously to control organ and body size. We propose a signal cascade for the control of body size that involves a germ-line signal, cGMP, G-kinase EGL-4 and DBL-1/TGFbeta pathway. It is interesting that two important pathways involving cGMP and TGFbeta, respectively, are related. Also, the results suggest a novel mechanism for the control of organ and body size in which hypodermis plays a key role