Mutations in insulin signaling pathway alter juvenile hormone synthesis in Drosophila melanogaster

Juvenile hormone (JH) is a key endocrine regulator of insect metamorphosis, reproduction, and aging. The synthesis of JH is regulated by neuropeptides and biogenic amines, but the molecular and cellular basis of this control remains largely unknown. Genetic analysis of JH synthesis in Drosophila melanogaster mutant for insulin signaling may provide new and powerful insights. Mutants of the insulin receptor (InR) are slow to develop, small, infertile, and long-lived. We previously reported that mutants of InR had reduced JH synthesis as young adults, and that normal longevity and vitellogenesis were restored by topical application of a JH analog [Science 292 (2001) 107]. Here, we describe the 10-day adult age course of JH synthesis from isolated corpus allatum (CA) of InR and of chico, the insulin receptor substrate homolog. JH synthesis increased in wildtype flies to a maximum of 30 fmol/gland/h at day 10. In contrast, homozygous InR mutants produced no more than 3 fmol/gland/h JH within the first 5 days, and only 7 fmol/gland/h at day 10. InR mutation disproportionately reduced the synthesis of JH III-bisepoxide, the major JH subtype of the fly. Mutation of chico also reduces body size and extends longevity [Science 292 (2001) 104; Aging Cell I (2002a) 75]. Both homozygous and heterozygous chico genotypes reduced JH synthesis, but only to 47 and 67%, respectively, of wildtype and without influencing the ratio of JH subtypes. Because JH synthetic rate does not correlate with the size of CA, it is not likely that insulin signaling mediates JH by impeding endocrine tissue development. Alternatively, we find allatotropin-positive axons to be abundant in the adult brain and in the corpora cardiaca-corpus allatum complex but these neurons are less immunoreactive in the InR mutant genotype, suggesting that insulin signaling may affect JH synthesis through control of JH regulatory neuropeptides. (c) 2005 Published by Elsevier Inc.