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A genetic screen for modifiers of drosophila Src42A identifies mutations in Egfr, rolled and a novel signaling gene
1Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas 66045, USA.
Abstract:
Drosophila Src42A, a close relative of the vertebrate c-Src, has been implicated in the Ras-Mapk signaling cascade. An allele of Src42A, Su(Raf)1, dominantly suppresses the lethality of partial loss-of-function Raf mutations. To isolate genes involved in the same pathway where Src42A functions, we carried out genetic screens for dominant suppressor mutations that prevented Su(Raf)1 from suppressing Raf. Thirty-six mutations representing at least five genetic loci were recovered from the second chromosome. These are Drosophila EGF Receptor (Egfr), rolled, Src42A, and two other new loci, one of which was named semang (sag). During embryogenesis, sag affects the development of the head, tail, and tracheal branches, suggesting that it participates in the pathways of Torso and DFGF-R1 receptor tyrosine kinases. sag also disrupts the embryonic peripheral nervous system. During the development of imaginal discs, sag affects two processes known to require Egfr signaling: the recruitment of photoreceptor cells and wing vein formation. Thus sag functions in several receptor tyrosine kinase (RTK)-mediated processes. In addition, sag dominantly enhances the phenotypes associated with loss-of-function Raf and rl, but suppresses those of activated Ras1(V12) mutation. This work provides the first genetic evidence that both Src42A and sag are modulators of RTK signaling.
Insights
Genetic screens identified new genes, including semang (sag), that modulate receptor tyrosine kinase (RTK) signaling pathways in Drosophila. These findings reveal novel components of RTK-mediated developmental processes.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Drosophila Src42A, analogous to vertebrate c-Src, is involved in Ras-Mapk signaling.
- A Src42A allele, Su(Raf)1, suppresses lethal mutations in Raf.
- Understanding Src42A's pathway requires identifying interacting genes.
Purpose of the Study:
- To isolate genes acting in the same pathway as Src42A.
- To identify novel modulators of receptor tyrosine kinase (RTK) signaling.
Main Methods:
- Genetic screens for dominant suppressors of Su(Raf)1's effect on Raf mutations.
- Analysis of mutations affecting Drosophila embryogenesis and imaginal disc development.
- Investigating the genetic interactions of identified loci with known signaling components.
Main Results:
- Thirty-six mutations at five loci were recovered, including Drosophila EGF Receptor (Egfr), rolled (rl), Src42A, and two new loci, semang (sag).
- sag mutations impact embryonic development (head, tail, tracheal branches) and peripheral nervous system formation, suggesting roles in Torso and DFGF-R1 RTK pathways.
- sag affects Egfr-dependent processes in imaginal discs, such as photoreceptor recruitment and wing vein formation.
- sag exhibits complex genetic interactions, enhancing Raf and rl loss-of-function phenotypes while suppressing activated Ras1(V12).
Conclusions:
- Src42A and sag are identified as modulators of RTK signaling in Drosophila.
- sag plays a significant role in multiple RTK-mediated developmental processes.
- This study provides crucial genetic evidence for the involvement of Src42A and sag in RTK pathways.