Abstract
Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism.
Highlights
Recent work has revealed multiple features of evolutionary conservation in endocrine regulation of glucose metabolism
Genetic studies reveal that Notch signaling restricts the number of corpora cardiaca progenitors, and we show that Notch signaling inactivation results in significant expansion of corpora cardiac cells
DrosDel deficiency lines used in this study cover only,50% of Drosophila genome, we successfully identified several genes previously not implicated in CC cell development
Summary
Recent work has revealed multiple features of evolutionary conservation in endocrine regulation of glucose metabolism. In the fruit fly Drosophila melanogaster, insulin-producing cells (IPCs) in the brain and adipokinetic hormone-producing corpora cardiaca (CC) cells in the neuroendocrine ring gland are the respective functional orthologues of mammalian pancreatic bcells and a-cells [1,2,3,4]. Insect CC cells resemble neurons in multiple ways; CC cells are peptidergic secretory cells [5] that harbor dense core vesicles [6], and have axon-like projections to vascular, gut and brain targets [3,4,7]. Similar to pancreatic islet cells and neuronal cell subsets, CC cells use KATP channels to regulate AKH secretion [3]. The molecular and physiological mechanisms governing CC endocrine function are strikingly similar to those of vertebrate pancreatic islets and neuroendocrine cells
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