Increased Insulin/Insulin Growth Factor Signaling Advances the Onset of Metamorphosis in Drosophila

Magdalena A Walkiewicz,Michael Stern,Andreas Bergmann

doi:10.1371/journal.pone.0005072

Abstract

Mechanisms by which attainment of specific body sizes trigger developmental transitions to adulthood (e.g. puberty or metamorphosis) are incompletely understood. In Drosophila, metamorphosis is triggered by ecdysone synthesis from the prothoracic gland (PG), whereas growth rate is increased by insulin/insulin growth factor signalling (IIS). Transgene-induced activation of PI3K, the major effector of IIS, within the PG advances the onset of metamorphosis via precocious ecdysone synthesis, raising the possibility that IIS triggers metamorphosis via PI3K activation in the PG. Here we show that blocking the protein kinase A (PKA) pathway in the insulin producing cells (IPCs) increases IIS. This increased IIS increases larval growth rate and also advances the onset of metamorphosis, which is accompanied by precocious ecdysone synthesis and increased transcription of at least one ecdysone biosynthetic gene. Our observations suggest that IIS is regulated by PKA pathway activity in the IPCs. In addition, taken together with previous findings, our observations are consistent with the possibility that, in Drosophila, attainment of a specific body size triggers metamorphosis via the IIS–mediated activation of PI3K and hence ecdysone synthesis in the PG.

Highlights

In organisms such as Drosophila and mammals, growth occurs during an early juvenile phase, but at a certain age, organisms transition to non-growing, sexually mature adults
In Drosophila larvae, metamorphosis is triggered by the steroid hormone ecdysone [1], which is synthesized in the prothoracic gland (PG), whereas larval growth rate is increased by insulin-like peptides released from the insulin producing cells (IPCs) of the larval brain [2]
Inhibiting the PKA pathway in the insulin producing cells increases insulin signalling To evaluate the effects of altered insulin growth factor signalling (IIS) on growth rate and the timing of metamorphosis, we began by altering activity of genes of the protein kinase A (PKA) pathway within the insulin producing cells (IPCs)

Summary

Introduction

In organisms such as Drosophila and mammals, growth occurs during an early juvenile phase, but at a certain age (corresponding to metamorphosis and puberty, respectively), organisms transition to non-growing, sexually mature adults. Genetic ablation of the IPCs, or a partial loss of function mutation in the single insulin receptor InR, each decreased IIS and growth rate, and delayed metamorphosis [2,3], suggesting that metamorphosis is activated by an IISresponsive process. Neither this process nor this IISresponsive tissue was identified, and it was not clear from these experiments to what extent IIS was rate limiting for developmental progression. It was not clear to what extent the effects of transgene-induced alterations in PI3K would mirror the response of a genetically wildtype PG to altered IIS

Methods

Results

Conclusion