Specification of Drosophila Corpora Cardiaca Neuroendocrine Cells from Mesoderm Is Regulated by Notch Signaling

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.

Suppression of Insulin Production and Secretion by a Decretin Hormone

“…Lst-GAL4 mediated expression of mCD4::tdTomato co-localized with Adipokinetic hormone (AKH) in corpora cardiaca (CC) cells (Figure 3A). The CC cells comprise 14 gut-associated endocrine cells which send projections to the midgut and secrete hormones into the circulation from projections to the dorsal vessel (Cognigni et al, 2011; Kim and Rulifson, 2004; Park et al, 2011). CC cells secrete AKH, a hormone thought to be a functional ortholog of mammalian glucagon, indicating that CC cell have roles analogous to preproglucagon-expressing cells in the mammalian pancreas and gastrointestinal tract (Kim and Rulifson, 2004; Park et al, 2011).…”

“…The CC cells comprise 14 gut-associated endocrine cells which send projections to the midgut and secrete hormones into the circulation from projections to the dorsal vessel (Cognigni et al, 2011; Kim and Rulifson, 2004; Park et al, 2011). CC cells secrete AKH, a hormone thought to be a functional ortholog of mammalian glucagon, indicating that CC cell have roles analogous to preproglucagon-expressing cells in the mammalian pancreas and gastrointestinal tract (Kim and Rulifson, 2004; Park et al, 2011). Lst protein co-localized with Akh, and with the dense-core vesicle marker ANF-EMD (Rao et al, 2001) in CC cell neurites ramifying on heart, consistent with the postulated role of Lst as a secreted hormone (Figure 3B, C).…”

The Insect Prothoracic Gland as a Model for Steroid Hormone Biosynthesis and Regulation

“…The regulatory group comprises a total of 13 DNA-binding proteins. Of these, molting defective ( mld ), vvl, ouija board ( ouib , aka CG11762 ), snail , and timeless ( tim ) were already known to have specific expression in the RG (Cheng et al, 2014; Danielsen et al, 2014; Komura-Kawa et al, 2015; Morioka et al, 2012; Neubueser et al, 2005;Sánchez-Higueras et al, 2014), while tinman has been linked to the embryonic development of the CC, but no expression in the RG has been demonstrated (Park et al, 2011). Among the identified transcription factors are Escargot, which is related to Snail, and Hand, which ranks among the 50 most highly enriched mRNAs in the RG (Table S2), as well as pdm3 , which encodes—like vvl —a POU-domain transcription factor.…”

Successive requirement of Glass and Hazy for photoreceptor specification and maintenance inDrosophila

“…509), 11 UAS-glass 9 and UAS-hazy (courtesy of J. Bischof) 37 . As a reporter for glass we used glass-DsRed flies (courtesy of S. Kim), which are also called glass5.2-RHS 21 . Flip-out misexpression experiments were performed as described previously 9 by using hsFLP; tub(FRTcassette)Gal4, UAS-lacZ.nls (courtesy of E. Piddini).…”