*JDC and WLH contributed equally to this work
In C. elegans, insulin/IGF signaling governs dauer formation, an alternative developmental pathway for animals under stress and starvation (reviewed in Hu, 2007). Conditional alleles of the sole insulin receptor gene,
daf-2, lead to constitutive activation of dauer program (Gems et al, 1998; Vowels and Thomas, 1992). With 40 insulin-like protein genes, they are proposed to function redundantly to modulate DAF-2 activity level, upon which the animal determine its developmental program (Pierce et al., 2001; Li et al., 2003). However, the cohort of insulin-like ligands in this process is determined. In this study, we report the identification of seven insulin-like ligands that constitute the major insulin signaling inputs through which DAF-2 determines dauer formation. We have deciphered their maturation processes, cellular origins, as well as sites of action. We show that these ligands are processed by two different proprotein convertases, function through both overlapping and non-overlapping cells, and cannot functionally replace each other. Their differential functions and processing suggest multiple levels of regulation for dauer formation.
Gems, D., Sutton, A.J., Sunermeyer, M.L., Albert, P.S., King, K.V., Edgley, M.,L., Larsen, P.L., and Riddle, D.L. (1998). Genetics, 150, 129. Hu, PJ (2007) Wormbook. Li, W., Kennedy, S.G. and Ruvkun, G. (2003) Genes Dev., 17, 844. Pierce, S.B., Costa, M., Wisotzkey, R., Devadhar, S., Homburger, S.A., Buchman, A.R., Ferguson, K.C., Heller, J., Platt, D.M., Pasquinelli, A.A., Liu, L.X., Doberstein, S.K. and Ruvkun, G. (2001). Genes Dev., 15, 672. Vowels, JJ and Thomas, J. (1992) Genetics 130, 105.