The EGF receptor and N signalling pathways act antagonistically in Drosophila mesothorax bristle patterning

An early step in the development of the large mesothoracic bristles (macroc haetae) of Drosophila is the expression of the proneural genes of the achae te-scute complex (AS-C) in small groups of cells (proneural clusters) of th e wing imaginal disc, This is followed by a much increased accumulation of AS-C proneural proteins in the cell that will give rise to the sensory orga n, the SMC (sensory organ mother cell). This accumulation is driven by cis- regulatory sequences, SMC-specific enhancers, that permit self-stimulation of the achaete, scute and asense proneural genes. Negative interactions amo ng the cells of the cluster, triggered by the proneural proteins and mediat ed by the Notch receptor (lateral inhibition), block this accumulation in m ost cluster cells, thereby limiting the number of SMCs, Here we show that t he proneural proteins trigger, in addition, positive interactions among cel ls of the cluster that are mediated by the Epidermal growth factor receptor (EGPR) and the Ras/Raf pathway. These interactions, which we denominate 'l ateral co-operation', are essential for macrochaetae SMC emergence. Activat ion of the EGFR/Ras pathway appears to promote proneural gene self-stimulat ion mediated by the SMC-specific enhancers. Excess EGFR signalling can over rule lateral inhibition and allow adjacent cells to become SMCs and sensory organs. Thus, the EGPR and Notch pathways act antagonistically in notum ma crochaetae determination.