Institut für Entwicklungsbiologie, Universität zu Köln, Gyrhofstr. 17, D-50923 Köln, Germany.
The development of most external sensory organs of the adult fly is controlled by the proneural genes achaete (ac) and scute (sc) and their activity defines proneural cell clusters in the imaginal discs. Upon mutual inhibition mediated by the Notch signalling pathway an individual cell within each cluster will become a sensory organ precursor cell (SOP). This restriction of proneural gene function and of the neural fate in a proneural cluster depends on the ability of the prospective SOP to prevent the surrounding cells from entering the neural developmental pathway.
Ectopic expression of the proneural genes sc or lethal of scute (l´sc) in the wing imaginal disc causes the development of ectopic bristles on the notum. Unexpectedly, a continuous level of ectopic l´sc transcription is not sufficient to determine a neural fate for any given ectodermal cell. Rather it appears that ectopic proneural clusters are created, which single out only few of their cells to become ectopic SOPs. This requires that mutual inhibition occurs between the cells of the ectopic proneural clusters. Consequently, the dominant phenotype is modified by mutations in genes known to be involved in neurogenesis.
To identify further elements of the regulatory network, we have used a Gal4 activator line with an expression pattern limited to the scutellar anlage. l´sc expression driven by this activator leads to supernumerary bristles on the scutellum. This dominant, quantifiable phenotype has been used to carry out a mutagenesis experiment for dominant enhancers and suppressors, i.e. mutations modifying the number of ectopic bristles in heterozygosity. In this way about 100,000 progeny of EMS or X-ray treated flies have been analysed to uncover autosomal genes involved in regulation of the neural fate. In addition 1,900 chromosomes carrying lethal P-element insertions were screened for modifiers.
Mutations were recovered in all autosomal genes known to be involved in neurogenesis and expected to modify the phenotype caused by ectopic expression of proneural genes: daughterless, extramacrochaetae, hairy, Delta, mastermind and Hairless. Moreover, we have isolated groups of non-complementing alleles for 10 genes so far not known to be involved in neurogenesis. Most of these mutations behave as enhancers of the ectopic bristle number, the expected function of the wildtype alleles is to downregulate proneural functions during neurogenesis. Our aim is to characterise these genes molecularly and functionally.