Abstract

Developmental transitions are often triggered by a neuroendocrine axis and can be contingent upon multiple organs achieving sufficient growth and maturation. How the neurodendocrine axis senses the size and maturity of peripheral organs is not known. In Drosophila larvae, metamorphosis is triggered by a sharp increase in the level of the steroid hormone ecdysone, secreted by the prothoracic gland (PG). Here, we show that the BMP2/4 ortholog Dpp can function as a systemic signal to regulate developmental timing. Dpp from peripheral tissues, mostly imaginal discs, can reach the PG and inhibit ecdysone biosynthesis. As the discs grow, reduced Dpp signaling in the PG is observed, consistent with the possibility that Dpp functions in a checkpoint mechanism that prevents metamorphosis when growth is insufficient. Indeed, upon starvation early in the third larval instar, reducing Dpp signaling in the PG abrogates the critical-weight checkpoint which normally prevents pupariation under these conditions. We suggest that increased local trapping of morphogen within tissues as they grow would reduce circulating levels and hence provide a systemic readout of their growth status.

Highlights

  • Organismal development is often orchestrated by a neuroendocrine axis, such as the hypothalamic–pituitary axis in mammals

  • Consistent with the known ability of Dpp to spread within tissues, expression of dpp, but not tkvQD, increased Dpp signaling beyond the wing pouch in the wing disc, as assessed by increased nuclear phosphorylated Mad (Fig 1E–G, arrowheads in Fig 1F and G)

  • We found that when dpp was overexpressed in a variety of peripheral tissues using different driver lines, pupariation was always delayed suggesting that Dpp can reach the prothoracic gland (PG) from a variety of locations in the larva (Fig S2A–G)

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Summary

Introduction

Organismal development is often orchestrated by a neuroendocrine axis, such as the hypothalamic–pituitary axis in mammals. Mechanisms likely exist by which the growth and maturation of peripheral organs are monitored by the neuroendocrine axis before important developmental transitions. In most cases, these mechanisms remain undefined. The onset of metamorphosis in Drosophila is a dramatic developmental transition which lends itself to genetic analysis (reviewed by Yamanaka et al [2013], Boulan et al [2015]). The larva is capable of feeding and acquiring additional nutrients for growth until it achieves its final size. The pupa is essentially a closed system where any new growth and tissue remodeling can only occur either by mobilizing stored nutrients or by the breakdown of larval tissues.

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