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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
Signalling by the sevenless protein tyrosine kinase is mimicked by Ras1 activation
M E Fortini1, M A Simon, G M Rubin
1Howard Hughes Medical Institute, University of California, Berkeley 94720.
Abstract:
Cell-fate specification of R7 photoreceptors in the developing Drosophila eye depends on an inductive signal from neighbouring R8 cells. Mutations in three genes, sevenless (sev), bride-of-sevenless (boss) and seven-in-absentia (sina) cause the R7 precursor to become a non-neural cone cell. The sev gene encodes a receptor protein tyrosine kinase (Sev) localized on the R7 surface, activated by a boss-encoded ligand presented by R8. The sina gene encodes a nuclear factor required in R7. Reduction in the dosage of the Ras1 gene impairs Sev-mediated signalling, suggesting that activation of Ras1 may be an important consequence of Sev activation. We report here that Ras1 activation may account for all of the signalling action of Sev; an activated Ras1Va112 protein rescues the normal R7 precursor from transformation into a cone cell in sev and boss null mutants and induces the formation of supernumerary R7 cells. Similar activation of the Drosophila Ras2 protein does not produce these effects, demonstrating Ras protein specificity.
Insights
Ras1 activation is crucial for Drosophila R7 photoreceptor development, mediating signals from the sevenless receptor. Activating Ras1 rescues R7 cell fate and can induce extra R7 cells, showing Ras protein specificity.
Area of Science:
- Developmental biology
- Cell signaling
- Genetics
Background:
- R7 photoreceptor cell-fate specification in Drosophila is a model for understanding receptor tyrosine kinase signaling.
- The sevenless (sev) receptor, activated by the bride-of-sevenless (boss) ligand, is essential for R7 development.
- Ras1 signaling is implicated in sev-mediated cell fate determination.
Purpose of the Study:
- To investigate the role of Ras1 activation in sevenless (Sev) signaling during Drosophila R7 photoreceptor development.
- To determine if Ras1 activation is sufficient to mediate all signaling functions of Sev.
- To assess the specificity of Ras protein involvement in this pathway.
Main Methods:
- Utilized Drosophila genetic mutants (sev, boss null mutants).
- Introduced activated Ras1Va112 protein into R7 precursors.
- Observed the effects of Ras1 activation on R7 cell fate and supernumerary R7 cell formation.
- Compared the effects of Ras1 activation with Ras2 activation.
Main Results:
- Activated Ras1Va112 rescued R7 precursors in sev and boss null mutants, preventing their transformation into cone cells.
- Activated Ras1Va112 induced the formation of supernumerary R7 cells.
- Activation of Drosophila Ras2 protein did not yield similar results, indicating specificity.
Conclusions:
- Ras1 activation is sufficient to account for the signaling activity of the sevenless receptor.
- Ras1 acts downstream of Sev and Boss in the R7 cell-fate specification pathway.
- The study highlights the specific role of Ras1 in mediating inductive signaling for photoreceptor development.
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