THE DROSOPHILA EMBRYONIC MIDLINE IS THE SITE OF SPITZ PROCESSING, ANDINDUCES ACTIVATION OF THE EGF RECEPTOR IN THE VENTRAL ECTODERM

The Drosophila EGF receptor (DER) is activated by secreted Spitz to in duce different cell fates in the ventral ectoderm. Processing of the p recursor transmembrane Spitz to generate the secreted form was shown t o be the limiting event, but the cells in which processing takes place and the mechanism that may generate a gradient of secreted Spitz in t he ectoderm were not known. The ectodermal defects in single minded (s im) mutant embryos, in which the midline fails to develop, suggested t hat the midline cells contribute to patterning of the ventral ectoderm . This work shows that the midline provides the site for Spitz express ion and processing. The Rhomboid and Star proteins are also expressed and required in the midline. The ectodermal defects of spitz, rho or S tar mutant embryos could be rescued by inducing the expression of the respective normal genes only in the midline cells, Rho and Star thus f unction non-autonomously, and may be required for the production or pr ocessing of the Spitz precursor. Secreted Spitz is the only sim-depend ent contribution of the midline to patterning the ectoderm, since the ventral defects observed in sim mutant embryos can be overcome by expr ession of secreted Spitz in the ectoderm. While ectopic expression of secreted Spitz in the ectoderm or mesoderm gave rise to ventralization of the embryo, increased expression of secreted Spitz in the midline did not lead to alterations in ectoderm patterning. A mechanism for ad justment to variable levels of secreted Spitz emanating from the midli ne may be provided by Argos, which forms an inhibitory feedback loop f or DER activation. The production of secreted Spitz in the midline, ma y provide a stable source for graded DER activation in the ventral ect oderm.