A screen for mutations that prevent lethality caused by expression of activated sevenless and Ras1 in the Drosophila embryo

Ras1 plays a critical role in receptor tyrosine kinase (RTK) signal transdu ction pathways that function during Drosophila development. We demonstrate that mis-expression of constitutively active forms of Ras1 (Ras1(V12)) and the Sevenless (Sev) RTK (Sev(S11)) during embryogenesis causes lethality du e to inappropriate activation of RTK/Ras1 signaling pathways. Genetic and m olecular data indicate that the rate of Sev(S11)/sev-Ras1(V12) lethality is sensitive to the expression level of both transgenes. To identify genes th at encode components of RTK/Ras1 signaling pathways or modulators of RNA po lymerase II transcription, we took advantage of the dose-sensitivity of the system and screened for second site mutations that would dominantly suppre ss the lethality. The collection of identified suppressors includes the PR5 5 subunit of Protein Phosphatase 2A indicating that downstream of Sev and R as 1 this subunit acts as a negative regulator of phosphatase activity. The isolation of mutations in the histone deacetylase RPD3 suggests that it fu nctions as positive regulator of sev enhancer-driven transcription. Finally , the isolation of mutations in the Trithorax group gene devenir and the ch aracterized allelism with the Breathless RTK encoding gene provides evidenc e for Ras1-mediated regulation of homeotic genes. Dev. Genet. 23:347-361, 1 998. (C) 1998 Wiley-Liss, Inc.dagger