The current state of knowledge concerning cis-regulatory sequences of the proneural genes of vertebrates and Drosophila is discussed. Many proneural genes have a complex modular arrangement of discrete enhancer elements. One unusual feature of these genes is that many distant enhancer elements, regulating expression in specific spatial locations, require input from previously synthesized protein from the proneural gene itself, in addition to other transcriptional activators. This is distinct from the auto-regulation, via E boxes in the promoter, that takes place in neural precursors. The selection of neural precursors from a field of cells expressing a proneural gene, is mediated by Notch signalling and requires up-regulation of proneural gene expression in the precursor concurrently with down-regulation in the surrounding cells. Although the way in which a single cell is selected remains unclear, a number of feedback loops have been uncovered that reinforce the choice. These are briefly surveyed. A specific regulatory element, the Sensory Organ Precursor element, that mediates selection of the precursors of the large sensory bristles, has been described in Drosophila. We report the conservation of this sequence in Calliphora vicina, a higher fly. In contrast, no such sequence is seen in the achaete-scute complex of Anopheles gambiae, a basal Dipteran species. We suggest that this enhancer may have arisen during the evolution of the cyclorraphous flies and present a hypothesis for its possible function
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