Neuroendocrine control of morphogenesis

Abstract

Drosophila larvae undergo a dramatic change in body shape at the end of the larval growth period: the long, transparent, and flexible larval cuticle is remodeled into the short, tanned, and rigid puparium, the skin inside which higher dipteran larvae undergo metamorphosis. This body change is achieved by a series of stereotyped muscular contractions accompanied by structural sclerotization of the cuticle. While the onset of the whole metamorphosis program is known to be under the control of the hormone ecdysone, the molecular pathways mediating the downstream behavioral and morphogenetic processes are less understood. Serendipitously, we observed that larvae lacking the conserved relaxin-receptor like G-protein coupled receptor (GPCR), Lgr3, fail to shorten into the characteristic puparium form, so that their cuticle sclerotizes into an elongated larva-like puparium instead. Tissue and cell-type-specific RNAi experiments revealed that this Lgr3 activity is separable from its previously described role during larval development, where it has been shown to act in a subpopulation of CNS neurons to coordinate imaginal disc growth with developmental timing, in a Drosophila insulin-like peptide 8 (Dilp8)-dependent manner. Rather, our results indicate that Lgr3 acts in a distinct population of CNS neurons that respond to a strong developmentally-triggered pulse of carcass-derived Dilp8 peptide, which occurs within a 30-60-min window at the onset of pupariation. Hence, the peptide hormone Dilp8 and the neuronal GPCR Lgr3 constitute a new interorgan communication pathway controlling puparium morphogenesis.