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Regulation of Notch output dynamics via specific E(spl)-HLH factors during bristle patterning in Drosophila.

ABSTRACT: The stereotyped arrangement of sensory bristles on the adult fly thorax arises from a self-organized process, in which inhibitory Notch signaling both delimits proneural stripes and singles out sensory organ precursor cells (SOPs). A dynamic balance between proneural factors and Enhancer of split-HLH (E(spl)-HLH) Notch targets underlies patterning, but how this is regulated is unclear. Here, were identify two classes of E(spl)-HLH factors, whose expression both precedes and delimits proneural activity, and is dependent on proneural activity and required for proper SOP spacing within the stripes, respectively. These two classes are partially redundant, since a member of the second class, that is normally cross-repressed by members of the first class, can functionally compensate for their absence. The regulation of specific E(spl)-HLH genes by proneural factors amplifies the response to Notch as SOPs are being selected, contributing to patterning dynamics in the notum, and likely operates in other developmental contexts.

SUBMITTER: Couturier L

PROVIDER: S-EPMC6677740 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Regulation of Notch output dynamics via specific E(spl)-HLH factors during bristle patterning in Drosophila.

Couturier Lydie L Mazouni Khalil K Corson Francis F Schweisguth François F

Nature communications 20190802 1

The stereotyped arrangement of sensory bristles on the adult fly thorax arises from a self-organized process, in which inhibitory Notch signaling both delimits proneural stripes and singles out sensory organ precursor cells (SOPs). A dynamic balance between proneural factors and Enhancer of split-HLH (E(spl)-HLH) Notch targets underlies patterning, but how this is regulated is unclear. Here, were identify two classes of E(spl)-HLH factors, whose expression both precedes and delimits proneural ac ...[more]

PMID: 31375669

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Project description:Methylmercury (MeHg) is a ubiquitous environmental contaminant and neurotoxicant that has long been known to cause a variety of motor deficits. These motor deficits have primarily been attributed to MeHg targeting of developing neurons and induction of oxidative stress and calcium dysregulation. Few studies have looked at how MeHg may be affecting fundamental signaling mechanisms in development, particularly in developing muscle. Studies in Drosophila recently revealed that MeHg perturbs embryonic muscle formation and upregulates Notch target genes, reflected predominantly by expression of the downstream transcriptional repressor Enhancer of Split mdelta [E(spl)m?]. An E(spl)m? reporter gene shows expression primarily in the myogenic domain, and both MeHg exposure and genetic upregulation of E(spl)m? can disrupt embryonic muscle development. Here, we tested the hypothesis that developing muscle is targeted by MeHg via upregulation of E(spl)m? using genetic modulation of E(spl)m? expression in combination with MeHg exposure in developing flies. Developmental MeHg exposure causes a decreased rate of eclosion that parallels gross disruption of indirect flight muscle (IFM) development. An increase in E(spl) expression across the pupal stages, with preferential E(spl)m? upregulation occurring at early (p5) stages, is also observed. E(spl)m? overexpression in myogenic lineages under the Mef2 promoter was seen to phenocopy eclosion and IFM effects of developmental MeHg exposure; whereas reduced expression of E(spl)m? shows rescue of eclosion and IFM morphology effects of MeHg exposure. No effects were seen on eclosion with E(spl)m? overexpression in neural and gut tissues. Our data indicate that muscle development is a target for MeHg and that E(spl)m? is a muscle-specific mediator of this myotoxicity. This research advances our knowledge of the target pathways that mediate susceptibility to MeHg toxicity, as well as a potential muscle development-specific role for E(spl)m?.

Dataset Information

Regulation of Notch output dynamics via specific E(spl)-HLH factors during bristle patterning in Drosophila.

Publications

Regulation of Notch output dynamics via specific E(spl)-HLH factors during bristle patterning in Drosophila.

Similar Datasets

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