Zebrafish brd2a and brd2b are paralogous members of the bromodomain-ET (BET) family of transcriptional coregulators that show structural and expression divergence

<p>Abstract</p> <p>Background</p> <p>Brd2 belongs to the bromodomain-extraterminal domain (BET) family of transcriptional co-regulators, and functions as a pivotal histone-directed recruitment scaffold in chromatin modification complexes affecting signal-dependent transcription. Brd2 facilitates expression of genes promoting proliferation and is implicated in apoptosis and in egg maturation and meiotic competence in mammals; it is also a susceptibility gene for juvenile myoclonic epilepsy (JME) in humans. The <it>brd2 </it>ortholog in <it>Drosophila </it>is a maternal effect, embryonic lethal gene that regulates several homeotic loci, including Ultrabithorax. Despite its importance, there are few systematic studies of <it>Brd2 </it>developmental expression in any organism. To help elucidate both conserved and novel gene functions, we cloned and characterized expression of <it>brd2 </it>cDNAs in zebrafish, a vertebrate system useful for genetic analysis of development and disease, and for study of the evolution of gene families and functional diversity in chordates.</p> <p>Results</p> <p>We identify cDNAs representing two paralogous <it>brd2 </it>loci in zebrafish, <it>brd2a </it>on chromosome 19 and <it>brd2b </it>on chromosome 16. By sequence similarity, syntenic and phylogenetic analyses, we present evidence for structural divergence of <it>brd2 </it>after gene duplication in fishes. <it>brd2 </it>paralogs show potential for modular domain combinations, and exhibit distinct RNA expression patterns throughout development. RNA <it>in situ </it>hybridizations in oocytes and embryos implicate <it>brd2a </it>and <it>brd2b </it>as maternal effect genes involved in egg polarity and egg to embryo transition, and as zygotic genes important for development of the vertebrate nervous system and for morphogenesis and differentiation of the digestive tract. Patterns of <it>brd2 </it>developmental expression in zebrafish are consistent with its proposed role in <it>Homeobox </it>gene regulation.</p> <p>Conclusion</p> <p>Expression profiles of zebrafish <it>brd2 </it>paralogs support a role in vertebrate developmental patterning and morphogenesis. Our study uncovers both maternal and zygotic contributions of <it>brd2</it>, the analysis of which may provide insight into the earliest events in vertebrate development, and the etiology of some forms of epilepsy, for which zebrafish is an important model. Knockdowns of <it>brd2 </it>paralogs in zebrafish may now test proposed function and interaction with homeotic loci in vertebrates, and help reveal the extent to which functional novelty or partitioning has occurred after gene duplication.</p

CRF-Like Diuretic Hormone Negatively Affects Both Feeding and Reproduction in the Desert Locust, Schistocerca gregaria

Diuretic hormones (DH) related to the vertebrate Corticotropin Releasing Factor (CRF) have been identified in diverse insect species. In the migratory locust, Locusta migratoria, the CRF-like DH (CRF/DH) is localized in the same neurosecretory cells as the Ovary Maturating Parsin (OMP), a neurohormone that stimulates oocyte growth, vitellogenesis and hemolymph ecdysteroid levels in adult female locusts. In this study, we investigated whether CRF-like DH can influence feeding and reproduction in the desert locust, Schistocerca gregaria. We identified two highly similar S. gregaria CRF-like DH precursor cDNAs, each of which also encodes an OMP isoform. Alignment with other insect CRF-like DH precursors shows relatively high conservation of the CRF/DH sequence while the precursor region corresponding to OMP is not well conserved. Quantitative real-time RT-PCR revealed that the precursor transcripts mainly occur in the central nervous system and their highest expression level was observed in the brain. Injection of locust CRF/DH caused a significantly reduced food intake, while RNAi knockdown stimulated food intake. Therefore, our data indicate that CRF-like DH induces satiety. Furthermore, injection of CRF/DH in adult females retarded oocyte growth and caused lower ecdysteroid titers in hemolymph and ovaries, while RNAi knockdown resulted in opposite effects. The observed effects of CRF/DH may be part of a wider repertoire of neurohormonal activities, constituting an integrating control system that affects food intake and excretion, as well as anabolic processes like oocyte growth and ecdysteroidogenesis, following a meal. Our discussion about the functional relationship between CRF/DH and OMP led to the hypothesis that OMP may possibly act as a monitoring peptide that can elicit negative feedback effects