RESUMEN
Disruptions of normal Hox gene expression can lead to severe morphological defects, revealing a link between the regulation of Hox expression and pattern formation. Here, we explore these links, focusing on the impact of microRNA regulation on the expression of the Drosophila Hox gene Ultrabithorax (Ubx) during haltere development. Through a combination of bioinformatic and transcriptomic analyses, we identify the miR-310/313 cluster (miR-310C) as a candidate regulator of Ubx Several experiments confirm this. First, miR-310C and Ubx protein show complementary expression patterns in haltere imaginal discs; second, artificial activation of miR-310C expression in haltere discs leads to Ubx-like phenotypes. Third, expression of a fluorescent reporter bearing Ubx 3'UTR sequences is reduced when co-expressed with miR-310C Fourth, deletion of miR-310C leads to Ubx upregulation and changes the array of mechanosensory sensilla at the base of the haltere. Fifth, an artificial increase of Ubx levels within the miR-310C expression domain phenocopies the mechanosensory defects observed in miR-310C mutants. We propose that miR-310C-mediated repression delimits Ubx fine-grain expression, contributing to the sculpting of complex morphologies in the Drosophila haltere with implications for flight control. Our work reveals a novel role of microRNA regulation in the control of Hox gene expression with impact on morphology.
Asunto(s)
Proteínas de Drosophila/genética , Drosophila melanogaster/anatomía & histología , Drosophila melanogaster/genética , Regulación del Desarrollo de la Expresión Génica , Genes Homeobox , Proteínas de Homeodominio/genética , MicroARNs/metabolismo , Factores de Transcripción/genética , Alas de Animales/anatomía & histología , Regiones no Traducidas 3'/genética , Animales , Tipificación del Cuerpo/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/ultraestructura , Sitios Genéticos , Proteínas de Homeodominio/metabolismo , MicroARNs/genética , Mutación/genética , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción/metabolismo , Regulación hacia Arriba/genética , Alas de Animales/ultraestructuraRESUMEN
Sensory information is gradually processed within dedicated neural circuits to generate specific behaviors. In this issue, Yang et al. push technology boundaries to measure both voltage and calcium signals from subcellular compartments of genetically defined interconnected neurons and shed light on local neural computations critical for motion detection.
Asunto(s)
Calcio , Neuronas , LuzRESUMEN
Neurons are thought to acquire shapes and configurations consistent with the wiring optimization principle. A new study sheds light on the underlying molecular mechanisms by demonstrating that N-cadherin-mediated differential adhesion determines relative neurite positioning in developing columnar synaptic modules.
Asunto(s)
Cadherinas/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiología , Células Fotorreceptoras de Invertebrados/citología , AnimalesRESUMEN
The Drosophila Hox gene Ultrabithorax (Ubx) controls the development of thoracic and abdominal segments, allocating segment-specific features to different cell lineages. Recent studies have shown that Ubx expression is post-transcriptionally regulated by two microRNAs (miRNAs), miR-iab4 and miR-iab8, acting on target sites located in the 3' untranslated regions (UTRs) of Ubx mRNAs. Here, we show that during embryonic development Ubx produces mRNAs with variable 3'UTRs in different regions of the embryo. Analysis of the resulting remodelled 3'UTRs shows that each species harbours different sets of miRNA target sites, converting each class of Ubx mRNA into a considerably different substrate for miRNA regulation. Furthermore, we show that the distinct developmental distributions of Ubx 3'UTRs are established by a mechanism that is independent of miRNA regulation and therefore are not the consequence of miR-iab4/8-mediated RNA degradation acting on those sensitive mRNA species; instead, we propose that this is a hard-wired 3'UTR processing system that is able to regulate target mRNA visibility to miRNAs according to developmental context. We show that reporter constructs that include Ubx short and long 3'UTR sequences display differential expression within the embryonic central nervous system, and also demonstrate that mRNAs of three other Hox genes suffer similar and synchronous developmental 3'UTR processing events during embryogenesis. Our work thus reveals that developmental RNA processing of 3'UTR sequences is a general molecular strategy used by a key family of developmental regulators so that their transcripts can display different levels of visibility to miRNA regulation according to developmental cues.
