Neuroendocrine regulation of Drosophila metamorphosis requires TGFβ/Activin signaling

Abstract

SUMMARYIn insects, initiation of metamorphosis requires a surge in the production of the steroid hormone 20-hydroxyecdysone from the prothoracic gland, the primary endocrine organ of juvenile larvae. Here, we show that blocking TGF/Activin signaling, specifically in the Drosophila prothoracic gland, results in developmental arrest prior to metamorphosis. The terminal, giant third instar larval phenotype results from a failure to induce the large rise in ecdysteroid titer that triggers metamorphosis. We further demonstrate that activin signaling regulates competence of the prothoracic gland to receive PTTH and insulin signals, and that these two pathways act at the mRNA and post-transcriptional levels, respectively, to control ecdysone biosynthetic enzyme expression. This dual regulatory circuitry may provide a cross-check mechanism to ensure that both developmental and nutritional inputs are synchronized before initiating the final genetic program leading to reproductive adult development. As steroid hormone production in C. elegans and mammals is also influenced by TGF/Activin signaling, this family of secreted factors may play a general role in regulating developmental transitions across phyla.

Autocrine regulation of ecdysone synthesis by β3-octopamine receptor in the prothoracic gland is essential for Drosophila metamorphosis

“…Thus, PG-specific knockdown causes a stronger phenotype than complete loss of Tdc2 activity in whole animals. A similar situation has been reported in regulation of metamorphosis by Activin signaling (12). These phenomena can be explained by a model in which some compensatory changes in other mutant tissues rescue the PG-specific knockdown phenotype in null-mutant animals.…”

“…Insulin-like peptides (Ilps), members of another class of neuron-derived factors, activate PI3K in the PG, resulting in production of ecdysone biosynthetic proteins (8)(9)(10)(11). The Activin/transforming growth factor-β (TGF-β) signaling pathway is also required in the PG for the expression of PTTH and Ilps receptors, although to date it remains unclear which organ produces the ligand that acts on the PG (12).…”

TGF-β signaling in insects regulates metamorphosis via juvenile hormone biosynthesis

“…Thus, no significant relations between allatostatins and Myo have been identified. On the other hand, in the Drosophila prothoracic gland, knockdown of the Activin/Babo/Smox pathway causes developmental arrest before metamorphosis through the control the ecdysone biosynthesis through the regulation of PTTH and insulin-signaling pathways (34). Our results show that Fig.…”

Nitric oxide directly regulates gene expression during Drosophila development: need some gas to drive into metamorphosis?: Figure 1.

“…Notably, when the expression levels of these factors in the PG are manipulated in a way that suppresses bFTZ-F1 expression, the animals fail to initiate metamorphosis and instead continue to feed and form giant larvae that have high levels of fat accumulation (Cáceres et al 2011). Since this ''huge permanent larva'' phenotype is commonly observed in ecdysteroidogenesis-deficient third instar larvae (Berreur et al 1984;Gibbens et al 2011) and can be rescued by ecdysone feeding (Cá ceres et al 2011), the present study clearly indicates that NO-mediated E75 inactivation in the PG is necessary to promote ecdysteroidogenesis, which in turn triggers appropriate behavioral and metabolic changes (from fat storage to fat utilization) necessary for metamorphosis.…”