Drosophila melanogaster uses bristles as mechnosensory organs that develop from sensory organ precursors (SOPs). According to the Prepattern Hypothesis, SOP development is regulated sequentially by three groups of genes. Firstly, prepattern genes set up spatial and temporal coordinates, and regulate expression of the second regulatory group called Proneural genes. In wing discs, the proneural genes achaete-scute complex (ASC) confer on cells a SOP potential and define neurogenic regions called proneural clusters. Although all proneural cluster cells have the neurogenic potential, only one or two cells in each cluster are selected to adopt the final SOP fate through a competition mechanism called lateral inhibition, which requires the function of the third regulatory group called neurogenic genes. Neurogenic genes suppress neurogenic potential by activating the Notch (N) signaling pathway.
Ectopic SOP formation associated with a single regulatory gene mutation is typically either spatially discontinuous or restricted to proneural cluster areas. We previously identified a novel type of ectopic SOP formation associated with knock-down of the gene fred. The ectopic SOPs display a spatially continuous pattern and are not limited to the proneural cluster areas. We have used microarray and yeast two-hybrid approaches to find genes involved in the fred regulatory network. The microarray analysis identified a number of genes misregulated by knock-down of fred. Some important prepattern genes, such as pannier (pnr), are downregulated in fred background. This is unexpected, as pnr gene function is required for SOP formation in medial notum region. We investigated the significance of pnr in fred regulatory machinery and identified a similar dual role for pnr in SOP formation. While pnr is required for proneural cluster and endogenous SOP formation in its regulatory region, it also cooperates with fred to suppress SOP fate outside proneural clusters. From the mis-regulated gene list, we identified another gene cullin-2, whose knock-down results in a similar ectopic SOP phenotype.
In this novel type of ectopic SOP development, the spatially continuous SOP pattern indicates a lack of lateral inhibition and N signaling, while the SOP formation outside proneural clusters indicates the removal of neurogenic suppression in non-neurogenic regions. Here, we show that two distinct ASC levels exist as thresholds for different neurodevelopmental processes. The ectopic SOP formation coupled with lack of N signaling and absence of proneural clusters may result from a low level of ASC expression, which represents a neurogenic potential that is otherwise suppressed by fred machinery in most wild type wing disc cells. On the other hand, proneural cluster formation and N signaling activation require higher ASC levels, which need positive regulations from fred and prepattern genes. Base on our observations and analysis, we propose a pre-proneural state hypothesis. Before prepattern genes define compartments in the wing disc, a neurogenic potential is present in all disc cells. In the wild type wing disc, the neurogenic potential in cells is suppressed by fred through prepattern genes and other signal transducers. Our hypothesis provides new insights into neurogenesis in the imaginal discs.