EGFR/MAP kinase signaling during Drosophila development

Benny Shilo Arkadi Schwartz Eyal Schejter
Molecular Genetics, Weizmann Institute of Science, Rehovot

The dynamic activation profile of EGFR in the developing eye, and the restricted amount of ligand that is released by photoreceptor cells pose a challenge. Is EGFR activation sufficiently sustained and/or prominent, in order to reliably induce transcriptional activation that will define the required cell fates? We have undertaken a detailed dissection of the transcriptional responses to EGFR signaling during Drosophila eye imaginal disc development. Ets-domain transcription factors encoded by the pointed locus are universal downstream mediators of EGFR-based signaling. Full disruption of pointed (pnt) function revealed a photoreceptor recruitment phenotype, in which only R8 cells are present in the ommatidia of newly developed eye discs. Generation of mutant clones for the pntP1 or PntP2 isoforms alone showed the same phenotype as complete pnt disruption, thus demonstrating that each isoform is essential for photoreceptor recruitment. Further analysis showed that the two Pnt forms are activated in a sequential manner: MAPK phosphorylates and activates PntP2, which is only capable of inducing pntP1 transcription. Once expressed, PntP1 is constitutively active and sufficient to induce target genes essential for photoreceptor development. The induction of EGFR-target genes may thus rely on PntP1 protein stability and be sustained by its activity, beyond the time window where local MAPK activity is triggered by EGFR. This setting may be particularly suited for the developing eye, where a plethora of mechanisms restrict the level and duration of EGFR activation, in order to generate discrete bursts of activation, leading to successive recruitment of photoreceptor cells.









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