The origin of dorsoventral polarity in Drosophila

In Drosophila dorsoventral (DV) polarity arises during oogenesis when the oocyte nucleus moves from a central posterior to an asymmetrical anterior position. Nuclear movement is a symmetry-breaking step and establishes orthogonality between the anteroposterior and the DV axes. The asymmetrically anchored nucleus defines a cortical region within the oocyte which accumulates high levels of gurken messenger RNA (mRNA) and protein. Gurken is an ovarian-specific member of the transforming growth factor-alpha (TGF-alpha) family of secreted ligands. Secreted Gurken forms a concentration gradient that results in a dorsal-to-ventral gradient of EGF receptor activation in the follicle cells surrounding the oocyte. This leads to concentration-dependent activation or repression of target genes of the EGF pathway in the follicular epithelium. One outcome of this process is the restriction of pipe expression to a ventral domain that comprises 40% of the egg circumference. Pipe presumably modifies extracellular matrix components that are secreted by the follicle cells and are present at the ventral side of embryo after egg deposition. Here, they activate a proteolytic cascade that generates a gradient of the diffusible ligand, Spätzle. Spätzle activates the Toll receptor at the surface of the embryo that stimulates the nuclear uptake of the transcription factor Dorsal. This leads to a nuclear concentration gradient of Dorsal that specifies the cell types along the DV axis of the embryo.