Once inside the nucleus, the Dorsal protein acts as a morphogen and turns on or off the expression of different sets of genes depending on Dorsal’s concentration. The expression of each responding gene depends on its regulatory DNA— specifically, on the number and affinity of the binding sites that this DNA contains for Dorsal and other transcription regulators. In this way, the regulatory DNA interprets the positional signal provided by the nuclear Dorsal protein gradient, so as to define a D-V series of territories—distinctive bands of cells that run the length of the embryo. Most ventrally—where the nuclear concentration of Dorsal protein is highest—it switches on, for example, the expression of a gene called Twist, which is specific for mesoderm. Most dorsally, where the nuclear concentration of Dorsal protein is lowest, the cells switch on a gene called Decapentaplegic (Dpp). And in an intermediate region, where the nuclear concentration of Dorsal protein is high enough to repress Dpp but too low to activate Twist, the cells switch on another set of genes, including one called Short gastrulation (Sog) (Figure 21–27A).
Products of the genes directly regulated by the Dorsal protein generate in turn more local signals, which define finer subdivisions along the D-V axis. These signals act during cellularization and take the form of conventional extracellular
Figure 21–26 The concentration gradient of Dorsal protein in the nuclei of the blastoderm. In wild-type Drosophila embryos, the protein is present in the dorsal cytoplasm and absent from the dorsal nuclei; ventrally, it is depleted in the cytoplasm and concentrated in the nuclei. In a mutant in which the toll pathway is activated everywhere and not just ventrally, Dorsal protein is everywhere concentrated in the nuclei; the result is a ventralized embryo. conversely, in a mutant in which the toll signaling pathway is inactivated, Dorsal protein everywhere remains in the cytoplasm and is absent from the nuclei; the result is a dorsalized embryo. (From
S. roth, D. Stein and c. Nüsslein-Volhard, Cell 59:1189–1202, 1989. With permission from elsevier.) 1166 Chapter 21: Development of Multicellular Organisms (B) gradients of Dpp and Sog proteins dorsoventral territories are specifed signal proteins. In particular, Dpp codes for a secreted TGFβ-family protein, which forms a local morphogen gradient in the dorsal part of the embryo. Sog encodes another secreted protein that is produced by the neurogenic ectoderm (which gives rise to the nervous system) and acts as an antagonist of Dpp protein. The opposing diffusion gradients of these two signal proteins create a steep gradient of Dpp activity: the highest Dpp activity levels, in combination with certain other factors, cause development of the most dorsal tissue of all—an extraembryonic membrane. Intermediate levels cause development of dorsal epidermis; and the absence of Dpp activity allows the development of neurogenic ectoderm (Figure 21–27B).
a hierarchy of Inductive Interactions Subdivides the Vertebrate embryo
The molecular genetic analysis of Drosophila development has uncovered how a cascade of transcription regulators and signaling pathways subdivides the embryo. The same principle of progressive pattern refinement is used during the development of all animal embryos, including vertebrates. Remarkably, conservation is not restricted to the general strategy of pattern formation, but also extends to many of the molecules involved.
As mentioned previously, the earliest phases of vertebrate development are surprisingly variable, even between closely related species, and it is even hard to say precisely how the axes of an early fly embryo correspond to those of an early frog or mouse embryo. Nevertheless, we shall see that amid this display of evolutionary plasticity, some features of early development turn out to be highly