Abams is a member of the neprilysin family of metallopeptidases that affects signaling pathways during Drosophila melanogaster eye development. Christine Woods, Landry Nfonsom, Jennifer Curtiss. New Mexico State University, Las Cruces, NM.

   To better understand Drosophila melanogaster eye development, we used mRNAseq and microarray analyses to identify targets co-regulated by Eyeless (Ey) and Hedgehog (Hh), Decapentaplegic (Dpp) or Notch (N) signaling. From this work, we identified a novel gene: abnormally blistered and misshapen eyes (abams). The predicted protein encoded by abams is a member of the neprilysin family of metallopeptidases, although it lacks certain highly conserved catalytic residues, suggesting that it is not capable of peptidase activity. RNA interference of abams (using an abams^IR construct) resulted in smaller and misshapen adult eyes. Expression of the eye proneural factor Atonal (Ato) initiates ahead of the furrow in abams^IR eye discs. However, proneural enhancement of Ato in intermediate groups does not occur and very few R8 cells expressing Ato emerge from the furrow. Surprisingly, abams^IR eye tissue lacking R8s is still able to develop photoreceptors. Peptidases of the neprilysin family are involved in cleaving and thereby regulating activity of signaling peptides. During Drosophila eye development, Hh and Dpp signaling are responsible for initial activation of ato ahead of the furrow, while N signaling is required for ato upregulation in the furrow. In addition, ectopic Egfr activity has been shown to lead to photoreceptor development in the absence of R8 cells. Accordingly, abams RNAi resulted in premature hh and dpp expression as well as down-regulation of N signaling and up-regulation of Egfr signaling. Based on this data and the fact that Egfr is known to activate hh and dpp expression, we hypothesize that the Abams protein physically binds to signaling proteins in the N and/or Egfr pathway, thereby regulating Drosophila eye development. Current efforts involve using genetic, molecular and biochemical techniques to determine which specific component(s) of the N and/or Egfr pathway are being targeted by Abams.