Mad acts downstream of Dpp receptors, revealing a differential requirement for dpp signaling in initiation and propagation of morphogenesis in the Drosophila eye.

Decapentaplegic (Dpp), a member of the TGF-beta family of cytokines, has been implicated in many patterning processes in Drosophila, including the initial steps of pattern formation in the developing eye. We show that the Mothers against dpp (Mad) gene is required for dpp signaling during eye development. Clonal analysis demonstrates a cell-autonomous function for Mad and genetic interactions indicate that Mad is an essential component of the signal transduction pathway downstream of the Dpp receptors in responding cells. Mad-mediated dpp signaling is absolutely required for the initiation of the morphogenetic furrow in the eye, but has only a minor role in its subsequent propagation across the eye disc. We also present evidence for the repression of wingless transcription by dpp signaling.

Regulation of furrow progression in the Drosophila eye by cAMP-dependent protein kinase A.

The earliest physical sign of differentiation in the Drosophila retina is the passage of the morphogenetic furrow across the epithelium of the eye disc. Secreted factors encoded by hedgehog (hh) and decapentaplegic (dpp) have been implicated in propagation of the furrow and the subsequent initiation of photoreceptor differentiation. The morphogenetic furrow initiates at the posterior edge of the third larval instar eye imaginal disc. Its continued progression towards the anterior is believed to depend upon secretion of Hh protein by the differentiating clusters of photoreceptors that emerge posterior to the moving furrow. This progression is marked by the initiation of expression of the transforming growth factor-beta homologue Dpp in cells entering the furrow anteriorly, and loss of dpp expression in cells emerging posteriorly. Although the transmembrane protein encoded by the patched gene has been genetically implicated as the Hh receptor, the intercellular signalling pathways involved in these inductive processes remain uncharacterized. Here we show that the catalytic subunit of cyclic AMP-dependent protein kinase A (Pka-C1) is required for the correct spatial regulation of dpp expression during eye development. Loss of Pka-C1 function is sufficient to produce an ectopic morphogenetic wave marked by premature ectopic photoreceptor differentiation and non-autonomous propagation of dpp expression. Our results indicate that Pka-C1 lies in a signalling pathway that controls the orderly temporal progression of differentiation across the eye imaginal disc.

Confrontation of scabrous expressing and non-expressing cells is essential for normal ommatidial spacing in the Drosophila eye.

The establishment of neural precursor cells in Drosophila depends on cell-cell interactions and lateral inhibition. Scabrous (sca) is involved in this process by preventing an excess of cells from adopting a neural precursor fate. Specifically in eye development, Sca protein function has been implicated in the spacing pattern that is essential for the ordered appearance of the ommatidial array. During this process sca expression is restricted to neurogenic groups of cells and later to the neural precursors. We report that ectopic sca expression in the morphogenetic furrow results in a rough eye phenotype with oversized and fused ommatidia. These defects in adult eyes are due to the generation of too many ommatidial preclusters in the morphogenetic furrow. Strikingly, sca loss-of-function mutants have an almost identical phenotype. Our results suggest that Sca plays a positive role in establishing the spacing pattern within the furrow and that the quantitative difference in sca expression between neighboring groups of cells is a determining factor in this process. Ectopic expression of Sca also represses endogenous sca expression in the furrow, suggesting that Sca is involved in a feedback loop affecting its own transcription. Interestingly, sca shares homology to a group of extracellular matrix proteins that have been implicated in neuronal differentiation. We present a model for sca function based on its phenotypic and molecular features.

Giant lens, a gene involved in cell determination and axon guidance in the visual system of Drosophila melanogaster.

Mutations in the Drosophila gene giant lens (gil) affect ommatidial development, photoreceptor axon guidance and optic lobe development. We have cloned the gene using an enhancer trap line. Molecular analysis of gil suggests that it encodes a secreted protein with an epidermal-growth-factor-like motif. We have generated mutations at the gil locus by imprecise excision of the enhancer trap P-element. In the absence of gil, additional photoreceptors develop at the expense of pigment cells, suggesting an involvement of gil in cell determination during eye development. In addition, gil mutants show drastic effects on photoreceptor axon guidance and optic lobe development. In wildtype flies, photoreceptor axons grow from the eye disc through the optic stalk into the larval brain hemisphere, where retinal innervation is required for the normal development of the lamina and distal medulla. The projection pattern of these axons in the developing lamina and medulla is highly regular and reproducible. In gil, photoreceptor axons enter the larval brain but fail to establish proper connections in the lamina or medulla. We propose that gil encodes a new type of signalling molecule involved in the process of axon pathfinding and cell determination in the visual system of Drosophila.