Transcriptional regulation of neuropeptide and peptide hormone expression by theDrosophila dimmedandcryptocephalgenes

Abstract

SUMMARY The regulation of neuropeptide and peptide hormone gene expression is essential for the development and function of neuroendocrine cells in integrated physiological networks. In insects, a decline in circulating ecdysteroids triggers the activation of a neuroendocrine system to stimulate ecdysis, the behaviors used to shed the old cuticle at the culmination of each molt. Here we show that two evolutionarily conserved transcription factor genes, the basic helix-loop-helix (bHLH) gene dimmed (dimm)and the basic-leucine zipper (bZIP) gene cryptocephal (crc),control expression of diverse neuropeptides and peptide hormones in Drosophila. Central nervous system expression of three neuropeptide genes, Dromyosuppressin, FMRFamide-related and Leucokinin, is activated by dimm. Expression of Ecdysis triggering hormone (ETH) in the endocrine Inka cells requires crc; homozygous crc mutant larvae display markedly reduced ETH levels and corresponding defects in ecdysis. crcactivates ETH expression though a 382 bp enhancer, which completely recapitulates the ETH expression pattern. The enhancer contains two evolutionarily conserved regions, and both are imperfect matches to recognition elements for activating transcription factor-4 (ATF-4), the vertebrate ortholog of the CRC protein and an important intermediate in cellular responses to endoplasmic reticulum stress. These regions also contain a putative ecdysteroid response element and a predicted binding site for the products of the E74 ecdysone response gene. These results suggest that convergence between ATF-related signaling and an important intracellular steroid response pathway may contribute to the neuroendocrine regulation of insect molting.

Regulation of Secretory Protein Expression in Mature Cells by DIMM, a Basic Helix–Loop–Helix Neuroendocrine Differentiation Factor

“…DIMM is both a differentiation factor and a regulatory factor DIMM is required for the embryonic development of secretory peptide expression in diverse neuronal and endocrine cell lineages (Allan et al, 2003(Allan et al, , 2005Hewes et al, 2003;Gauthier and Hewes, 2006). In the current study, we extended these findings through spatiotemporal manipulation of dimm transgene expression.…”

Complex steroid–peptide–receptor cascade controls insect ecdysis

“…The presence of 1-2 putative CRC binding sites in the eth upstream region provides further evidence that CRC is directly involved in eth expression (Gauthier and Hewes, 2006). The basic helix-loop-helix gene dimm is also expressed in Inka cells and may participate in ETH synthesis (Hewes et al, 2003).…”

“…The CRC is a basic-leucine zipper transcription factor expressed in Inka cells (Hewes et al, 2000;Gauthier and Hewes, 2006). Using in situ hybridization technique, severely suppressed eth transcription was observed in crc mutant larvae, which resulted in ecdysis defects comparable with eth mutants lacking ETH.…”

Farnesoid secretions of dipteran ring glands: What we do know and what we can know

“…However, there are the recent molecular findings that (a) mutated USP ligand binding domain misfunctions so as to prevent proper larval body contraction just prior to pupariation (Henrich et al, 2000), and (b) that the USP ligand binding domain is functional to tightly bind to the methyl farnesoate product of the ring gland. These new data offer a conceptual framework in formulationof testable hypothesis on potential intersection of farnesoid signaling and ecdysone-associated eclosion pathways (Gauthier and Hewes, 2006).…”