DNA-binding protein Suppressor of Hairless [Su(H)] to activate transcription of the Enhancer of split complex [E(spl)-

The Drosophila external sensory (es) organ is an excellent model system to study cell fate specification. Its development involves multiple steps of cell fate determination, which are governed by combined effects of intrinsic and extrinsic signals. Eventually, these signals are transduced to the nucleus and integrated to change the state of gene expression that promotes a particular fate (Jan and Jan, 1994). In the formation of an es organ, the first step is expression of proneural genes in a small group of ectodermal cells, known as ‘proneural clusters’. achaete (ac) and scute (sc) are the proneural genes that promote es organ formation, and both genes encode basic helix-loop-helix (bHLH) transcriptional activators (for reviews, see Ghysen and Dambly-Chaudiere, 1988; Campuzano and Modollel, 1992). Although each cell in the proneural cluster is competent to form a neural precursor, these proneural-cluster cells compete with each other so that a single cell is selected to develop into a sensory organ precursor (SOP). The remaining cells are prevented from adopting the SOP neural fate by the process of lateral inhibition that involves cell-cell interaction (for reviews, see Greenwald, 1998; Artavanis-Tsakonas et al., 1999) mediated by the receptor Notch (N) and its ligand Delta. Upon ligand binding, the membrane receptor N is processed, and the intracellular domain (NICD) (Schroeter et al., 1998) is released from the membrane to the nucleus (Lecourtois and Schweisguth, 1998; Struhl and Adachi, 1998). NICD forms a complex with the DNA-binding protein Suppressor of Hairless [Su(H)] to activate transcription of the Enhancer of split complex [E(spl)C] (Bailey and Posakony, 1995; Lecourtois and Schweisguth, 1995). Members of the E(spl)-C down-regulate ac and sc expression in cooperation with the transcriptional repressor Groucho (Heitzler et al., 1996), thus leading to suppression of the SOP cell fate. In neurogenic mutants that disrupt this lateral inhibition process, supernumerary cells adopt SOP rather than alternative epidermal cell fate. An adult es organ (bristle) consists of four different daughter cells (neuron, sheath cell, hair cell and socket cell) that are generated through asymmetric division of a SOP cell (Gho and Schweisguth, 1998; Gho et al., 1999; Reddy and Rodrigues, 1999). After the first asymmetric division, the SOP cell produces two secondary precursors, IIa and IIb (see schematic drawing in Fig. 7A). The IIb cell again divides asymmetrically 2699 Development 128, 2699-2710 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV8780