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• W2766606789 endingPage "e0186439" @default.
• W2766606789 startingPage "e0186439" @default.
• W2766606789 abstract "Drosophila atonal (ato) is required for the specification of founding R8 photoreceptors during retinal development. ato is regulated via dual eye-specific enhancers; ato-3' is subject to initial induction whereas 5'-ato facilitates Notch-mediated autoregulation. Notch is further utilized to induce bHLH repressors of the E(spl) locus to restrict Ato from its initial broad expression to individual cells. Although Notch operates in two, distinct phases, it has remained unclear how the two phases maintain independence from one another. The difference in these two phases has attributed to the hypothesized delayed expression of E(spl). However, immunofluorescence data indicate that E(spl) are expressed during early Ato patterning, suggesting a more sophisticated underlying mechanism. To probe this mechanism, we provide evidence that although E(spl) exert no influence on ato-3', E(spl) repress 5'-ato and deletion of the E(spl) locus elicits precocious 5'-ato activity. Thus, E(spl) imposes a delay to the timing in which Ato initiates autoregulation. We next sought to understand this finding in the context of E(spl)D, which encodes a dysregulated variant of E(spl)M8 that perturbs R8 patterning, though, as previously reported, only in conjunction with the mutant receptor Nspl. We established a genetic interaction between E(spl)D and roughened eye (roe), a known modulator of Notch signaling in retinogenesis. This link further suggests a dosage-dependence between E(spl) and the proneural activators Ato and Sens, as indicated via interaction assays in which E(spl)D renders aberrant R8 patterning in conjunction with reduced proneural dosage. In total, the biphasicity of Notch signaling relies, to some degree, on the post-translational regulation of individual E(spl) members and, importantly, that post-translational regulation is likely necessary to modulate the level of E(spl) activity throughout the progression of Ato expression." @default.
• W2766606789 created "2017-11-10" @default.
• W2766606789 creator A5085556774 @default.
• W2766606789 creator A5090809707 @default.
• W2766606789 date "2017-10-16" @default.
• W2766606789 modified "2023-09-24" @default.
• W2766606789 title "Analysis of transient hypermorphic activity of E(spl)D during R8 specification" @default.
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• W2766606789 doi "https://doi.org/10.1371/journal.pone.0186439" @default.
• W2766606789 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5643056" @default.
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• W2766606789 hasPublicationYear "2017" @default.
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