EGFR Mediates Repulsive Signals

Abstract

The epidermal growth factor receptor (EGFR) is well known for mediating chemoattractant signals in epithelia. Gallio et al . report that in the Drosophila developing tracheal system, EGFR signaling mediates a repulsive signal. The gene encoding Rhomboid 3 (Rho3), a protease that activates EGFR ligands, was identified in a screen for mutants that caused midline crossing of ganglionic branches (GBs). GBs sprout from the lateral trunk of the trachea and migrate to invade the ventral nerve cord. In the null rho3 pllb mutant, GB midline crossing occurred with nearly complete penetrance; however, there were no defects in axonal midline crossing. Analysis of flies lacking slit and rho3 showed additive phenotypes, which suggests that slit and Rho3 act in separate repulsive pathways. Targeted expression of dominant-negative EGFR in GBs produced multiple GB migration defects. Targeted expression of Rho1, a protein closely related to Rho3, indicated that Rhomboid activity was required not in the GBs but in cells of the nervous system, which is consistent with the results of analysis of the expression of rho3 in situ. Analysis of flies with dominant-negative or activated forms of various signaling components indicated that Ras, but not Raf, phospholipase C, phosphoinositide 3-kinase, or the transcription factor Yan, were required to prevent midline crossing. Hyperactivation of the EGFR, Ras, or Rhomboid activity resulted in misrouting, but not in midline crossing, of GBs. The authors propose that the level of EGFR signaling provides a spatial cue that GBs use to determine distance from the midline. M. Gallio, C. Englund, P. Kylsten, C. Samakovlis, Rhomboid 3 orchestrates Slit-independent repulsion of tracheal branches at the CNS midline. Development 131 , 3605-3614 (2004). [Abstract] [Full Text]