Analysis of transient hypermorphic activity of E(spl)D during R8 specification
| Autor: | Ashok P. Bidwai, Adam T. Majot |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mutant lcsh:Medicine Sodium Phosphate Cell Signaling Basic Helix-Loop-Helix Transcription Factors Medicine and Health Sciences Drosophila Proteins lcsh:Science Notch Signaling Regulation of gene expression Multidisciplinary Drosophila Melanogaster musculoskeletal neural and ocular physiology 05 social sciences Gene Expression Regulation Developmental Signaling cascades Eukaryota Animal Models Phenotype Hedgehog signaling pathway Cell biology Insects Protein Transport Chemistry Phenotypes Enhancer Elements Genetic Experimental Organism Systems Physical Sciences Photoreceptor Cells Invertebrate Drosophila Anatomy Drosophila melanogaster psychological phenomena and processes Research Article Signal Transduction 050104 developmental & child psychology MAPK signaling cascades Arthropoda Notch signaling pathway Repressor Nerve Tissue Proteins Biology Research and Analysis Methods Phosphates 03 medical and health sciences Model Organisms Ocular System Genetics otorhinolaryngologic diseases Animals 0501 psychology and cognitive sciences Enhancer Immunohistochemistry Techniques lcsh:R Chemical Compounds Organisms Biology and Life Sciences Cell Biology biology.organism_classification Invertebrates Histochemistry and Cytochemistry Techniques 030104 developmental biology Genetic Loci Mutation Immunologic Techniques Hedgehog Signaling Eyes lcsh:Q sense organs Head |
| Zdroj: | PLoS ONE, Vol 12, Iss 10, p e0186439 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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