Gbb/BMP signaling is required to maintain energy homeostasis in Drosophila

Abstract

The coordination of animal growth and development requires adequate nutrients. During times of insufficient food, developmental progression is slowed and stored energy is utilized to ensure that cell and tissue survival are maintained. Here, we report our finding that the Gbb/BMP signaling pathway known to play an important role in many developmental processes in both vertebrates and invertebrates, is critical in the Drosophila larval fat body for regulating energy homeostasis. Animals with mutations in the Drosophila BMP-5,7 orthologue, glass bottom boat (gbb), or in its signaling components, display phenotypes similar to nutrient-deprived and Tor mutant larvae. These phenotypes include a developmental delay with reduced overall growth, a transparent appearance, and altered total lipid, glucose and trehalose levels. We find that Gbb/BMP signaling is required in the larval fat body for maintaining proper metabolism, yet interestingly, following nutrient deprivation larvae in turn show a loss of BMP signaling in fat body cells indicating that Gbb/BMP signaling is a central player in homeostasis. Finally, despite strong phenotypic similarities between nutrient-compromised animals and gbb mutants, distinct differences are observed in the expression of a group of starvation responsive genes. Overall, our results implicate Gbb/BMP signaling as a new pathway critical for positive regulation of nutrient storage and energy homeostasis during development.

Notch/Delta signalling is not required for segment generation in the basally branching insectGryllus bimaculatus

“…Moreover, we found that examining RNAi phenotypes at several different developmental time points and contrasting the results of maternal and zygotic knockdown studies were crucial to understanding the roles of Delta in cricket embryogenesis. Following the progression of the Dl RNAi phenotype over time allowed us to detect tissue-specific effects on neural development, as well as generic developmental delays, which are a common feature of lossof-function mutations in Notch pathway members (Ballard et al, 2010;Julian et al, 2010;Reis et al, 2011). These observations helped us to distinguish such neural and developmental delay phenotypes from specific effects on segmentation.…”

Crimpy inhibits the BMP homolog Gbb in motoneurons to enable proper growth control at theDrosophilaneuromuscular junction

“…If so, the NMJ overgrowth observed in cmpy LOF mutants should be suppressed by RNAimediated knockdown of Gbb in motoneurons. We first tested whether motoneuronal Gbb is necessary for normal NMJ growth by driving UAS-gbb RNAi (Ballard et al, 2010) in motoneurons using the D42Gal4 driver. D42Gal4/UAS-gbb RNAi larvae displayed wild-type numbers of boutons at NMJ 6/7 and NMJ 4 ( Fig.…”

Retrograde BMP signaling controls Drosophila behavior through regulation of a peptide hormone battery

“…However, it will be interesting to explore whether the incomplete rescue does in fact reflect a necessary contribution from other tissues. Gbb is a secreted protein that is widely expressed, such as by the fat body, somatic and visceral muscle, neurohemal organs and ring gland (Ballard et al, 2009;Doctor et al, 1992;Marques et al, 2003), and may circulate in the hemolymph. Ongoing studies aim to determine whether tissues in addition to muscle are necessary, sufficient or act redundantly to modulate BMP signaling in CCAP-ENs.…”

“…However, we do not rule out the possibility that other sources for Gbb exist, perhaps secreting the ligand into the circulating hemolymph. In this regard, it is notable that Ballard et al (Ballard et al, 2009) reported that, in gbb mutants, restoration of Gbb in another peripheral tissue, the fat body, failed to rescue BMP signaling in neurons, suggesting that distant signaling via the hemolymph is not sufficient. Further detailed analysis will be required to identify necessary and/or redundant roles for other tissues in neuronal BMP signaling.…”