GENES OF THE ENHANCER OF SPLIT AND ACHAETE-SCUTE COMPLEXES ARE REQUIRED FOR A REGULATORY LOOP BETWEEN NOTCH AND DELTA DURING LATERAL SIGNALING IN DROSOPHILA

Like the neuroblasts of the central nervous system, sensory organ prec ursors of the peripheral nervous system of the Drosophila thorax arise as single spaced cells. However, groups of cells initially have neura l potential as visualized by the expression of the proneural genes ach aete and scute. A class of genes, known as the 'neurogenic genes', fun ction to restrict the proportion of cells that differentiate as sensor y organ precursors. They mediate cell communication between the compet ent cells by means of an inhibitory signal. Delta, that is transduced through the Notch receptor and results in a cessation of achaete-scute activity, Here we show that mutation of either the bHLH-encoding gene s of the Enhancer of split complex (E(spl)-C) or groucho, like Notch o r Delta mutants, cause an overproduction of sensory organ precursors a t the expense of epidermis. The mutant cells behave autonomously sugge sting that the corresponding gene products are required for reception of the inhibitory signal. Epistasis experiments place both E(spl)- C b HLH-encoding genes and groucho downstream of Notch and upstream of ach aete and scute, consistent with the idea that they are part of the Not ch signalling cascade. Since all competent cells produce both the rece ptor and its ligand, it was postulated that Notch and Delta are linked within each cell by a feedback loop. We show, that, like mutant Notch cells, cells mutant for E(spl)-C bHLH-encoding genes or groucho inhib it neighbouring wild-type cells causing them to adopt the epidermal fa te. This inhibition requires the genes of the achaete-scute complex (A SC) which must therefore regulate the signal Delta. Thus there is a re gulatory loop between Notch and Delta that is under the transcriptiona l control of the E(spl)-C and ASC genes.