Pinning Down Positional Information: Dorsal–Ventral Polarity in the Drosophila Embryo

Can we now explain how a stable extracellular gradient is produced to define dorsal–ventral patterning in the Drosophila embryo? The DER pathway represses transcription of pipe, confining its transcription to those follicle cells that surround the ventral 30%–50% of the egg. Pipe protein in the same cells modifies a proteoglycan (be it Nudel or another protein) in a specific way so that it nucleates a ventral protein complex, perhaps on the plasma membrane of the embryo. Only when that ventral complex is properly assembled can the sequence of proteolytic activation events that produce active Spatzle begin. If activated Spatzle is produced on the ventral plasma membrane of the embryo, it will not have to diffuse any significant distance before it encounters Toll, its receptor on the plasma membrane. Tight binding to Toll would then preclude further diffusion of Spatzle to the other side of the embryo. Thus, if the active ligand can only be produced in a protein complex adjacent to Toll, ligand production and ligand presentation can be rigidly linked in space. It will be interesting to keep this mechanism of localized ligand activation in mind during characterization of the recently discovered human homologs of Toll and their functions in innate immune responses (Rock et al. 1998xRock, F.L, Hardiman, G, Timans, J.C, Kastelein, R.A, and Bazan, J.F. Proc. Natl. Acad. Sci. USA. 1998; 95: 588–593Crossref | PubMed | Scopus (1227)See all ReferencesRock et al. 1998).So far, so good. Mysteries, however, remain. The distribution of nuclear Dorsal in the embryo does not mirror the pattern of pipe transcription in the ovary. The distribution of pipe RNA in the follicle cells is broader than the high point of the Dorsal gradient: pipe RNA is found around 30%–50% of the egg circumference in apparently equal concentrations, and yet there is a gradient of Dorsal, with the highest concentrations of Dorsal found in 20%–25% of ventral nuclei in the embryo and detectable concentrations of nuclear Dorsal extending through the ventral 60% of the embryo. It will be important to examine the spatial distribution of Pipe protein, although it seems unlikely that the distribution of the protein will be graded in ventral follicle cells whereas the RNA is uniform. Instead, it is most likely that a later diffusion-dependent step determines the final shape of the Dorsal gradient.Perhaps the biggest puzzle is the embryonic phenotype seen in the absence of DER signaling, when pipe is expressed in all follicle cells. If Pipe directly dictated Dorsal nuclear localization, then all the nuclei in these embryos should have equivalent high concentrations of Dorsal. Although more nuclei have the maximal concentration of Dorsal, these embryos do have a Dorsal gradient. Most remarkably, as demonstrated by Roth and Schupbach 1994xRoth, S and Schupbach, T. Development. 1994; 120: 2245–2257PubMedSee all ReferencesRoth and Schupbach 1994, some of these embryos have two Dorsal gradients—two high points of nuclear Dorsal, each flanked by gradients of Dorsal of approximately the same slope as that seen in the wild-type embryo. These observations argue that Pipe defines the region of the embryo where ligand processing can occur, but other mechanisms determine how far the ligand can spread and where the peak of Dorsal activation will arise.