SPITZ AND WINGLESS, EMANATING FROM DISTINCT BORDERS, COOPERATE TO ESTABLISH CELL FATE ACROSS THE ENGRAILED DOMAIN IN THE DROSOPHILA EPIDERMIS

A key step in development is the establishment of cell type diversity across a cellular field. Segmental patterning within the Drosophila em bryonic epidermis is one paradigm for this process, At each parasegmen t boundary, cells expressing the Wnt family member Wingless confront c ells expressing the homeoprotein Engrailed, The Engrailed-expressing c ells normally differentiate as one of two alternative cell types, In i nvestigating the generation of this cell type diversity among the 2-ce ll-wide Engrailed stripe, we previously showed that Wingless, expresse d just anterior to the Engrailed cells, is essential for the specifica tion of anterior Engrailed cell fate, In a screen for additional mutat ions affecting Engrailed cell fate, we identified anterior open/yan, a gene encoding an inhibitory ETS-domain transcription factor that is n egatively regulated by the Ras1-MAP kinase signaling cascade, We find that Anterior Open must be inactivated for posterior Engrailed cells t o adopt their correct fate. This is achieved by the EGF receptor (DER) , which is required autonomously in the Engrailed cells to trigger the Ras1-MAP kinase pathway. Localized activation of DER is accomplished by restricted processing of the activating ligand, Spitz. Processing i s confined to the cell row posterior to the Engrailed domain by the re stricted expression of Rhomboid, These cells also express the inhibito ry ligand Argos, which attenuates the activation of DER in cell rows m ore distant from the ligand source, Thus, distinct signals flank each border of the Engrailed domain, as Wingless is produced anteriorly and Spitz posteriorly, Since we also show that En cells have the capacity to respond to either Wingless or Spitz, these cells must choose their fate depending on the relative level of activation of the two pathway s.