Direct downstream targets of proneural activators in the imaginal disc include genes involved in lateral inhibitory signaling.

Abstract

The body surface of the adult fly is covered with a complex array of multicellular sensory organs arranged in a largely invariant spatial pattern. In most cases, the cells comprising each of these organs are the progeny of a single sensory organ precursor (SOP) cell (Hartenstein and Posakony 1989). SOPs are determined during the late larval and early pupal stages within undifferentiated epithelial sheets, the imaginal discs and histoblast nests, that ultimately give rise to the cuticular structures of the adult. The process of establishing the pattern of cells committed to the SOP fate, and thus the pattern of sensory organs, consists of at least two major steps. First, the competence to acquire the SOP cell fate is conferred on small groups of cells by the spatially restricted expression and activity of certain proneural genes, which encode transcriptional activators of the basic-helixloop-helix (bHLH) class. Then, within each of these proneural clusters, all but one of the competent cells are inhibited from expressing the SOP fate by local cell-cell interactions that depend on the activity of a second set of Present addresses: 1Department of Molecular and Cell Biology,

phyllopod is a target gene of proneural proteins in Drosophila external sensory organ development

“…Ac and Sc are bHLH transcriptional activators, and Ac͞Da and Sc͞Da heterodimers bind specifically to the E boxes CAG(G͞C)TG with high affinity and CACGTG with low affinity (21). Within the 4.1-kb phyl promoter region, there are four such E boxes (E1-E3, CAGCTG; E4, CACGTG; Fig.…”

“…For example, senseless (sens) is expressed in SOPs and is required to maintain high levels of proneural proteins in SOPs (19,20). Genes involved in lateral inhibition to select SOPs are also targets for Ac and Sc, including scabrous (sca), Delta (Dl), and those in the Enhancer of split [E(spl)] and Bearded (Brd) complexes (21,22). However, target genes essential for SOP differentiation and the mechanism(s) by which they promote the differentiation process are relatively unknown.…”

Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling

“…This experiment has been performed on many signalregulated enhancers, including those activated by Notch, TGF-␤, Wnt, nuclear receptor, Jak/STAT, Hh, and RTK signaling, with the consistent result that cis-regulatory sequences besides SPREs are required for proper target gene expression (e.g., Danesch et al 1987;Schule et al 1988;Singson et al 1994;Giese et al 1995;Rothenberg and Ward 1996;Pearce et al 1998;Szuts et al 1998;Hepker et al 1999;Barolo et al 2000;Certel et al 2000;Flores et al 2000;Halfon et al 2000;Ramana et al 2000;Xu et al 2000;Affolter et al 2001;Knirr and Frasch 2001). For example, a wing margin enhancer of the Drosophila gene vestigial that is directly activated by Dpp/ TGF-␤ signaling via Mad also requires binding by the locally expressed activator Drifter for its function (Certel et al 2000).…”

“…Although local activators have not been identified for all signal-regulated developmental enhancers, no such enhancer has been found to rely solely on SPREs for its activity. Studies of Notch pathway target genes in Drosophila illustrate clearly how signal-regulated transcriptional activation by Su(H) is integrated with different local activator proteins to generate a variety of distinct expression patterns: (1) Synergistic activation requiring both Su(H) binding sites (Notch response elements) and sites for the proneural bHLH activators of the achaetescute complex is necessary for high levels of Enhancer of split complex gene expression in proneural clusters in the ectoderm (Singson et al 1994;Bailey and Posakony 1995;Nellesen et al 1999;Cooper et al 2000). (2) The single-minded gene, activated by the ventral determinants Dorsal and Twist as well as by Su(H), is expressed in Notch-responsive mesectodermal cells in the embryo (Morel and Schweisguth 2000).…”

“…(C) Partial sufficiency of proneural bHLH proteins as local activators expressed in proneural clusters, sites of active Notch signaling for the specification of sensory organ precursor cells (see inset to A). Shown is the pattern of expression of a lacZ reporter construct in which a minimal promoter is driven by four high-affinity E-box binding sites for proneural protein complexes (Van Doren et al 1991;Singson et al 1994;Singson 1995). Proneural bHLH activators are sufficient to elicit transcription of the reporter gene in a substantial subset of proneural cluster cells in the wing imaginal disc (cf.…”