My long-term objectives are 1) to identify the developmental processes transforming the unicellular organization of the egg of the vertebrate Xenopus laevis is into the multicellular organization of the embryo, particularly into the anteroposterior array of dorsal structures of the body axis; and 2) to understand the cell biological/molecular basis of these processes. We have examined three stage-specific processes for their roles in dorsal development: 1) cortical rotation of the egg in its first cell cycle, which changes the egg from cylindrical to bilateral symmetry, 2) formation of the Spemann organizer by inductions from vegetal and marginal zone cells in the blastula stages (""""""""organizing the organizer""""""""), and 3) functioning of the Spemann organizer in neural induction in the gastrula stage. Inhibition of any of these processes leads to the same syndrome of final developmental defects: truncation of the body aids from the anterior end, at a level defined by the extent of inhibition. Complete failure of any process results in radially ventralized embryos, with no body axis, a default pathway of development. Dorsalized embryos arise when these processes are exaggerated. The spectrum of dorsalized-ventralized anatomies, which may be general for vertebrates, contains forms similar to those of well known human birth defects such as cyclopia, microcephaly, and acephaly. In the request period, we will study each process further: For rotation, we will characterize the anchoring and directionality of the microtubules serving as tracks, and ask about the immediate local effect of rotation on the dorsal quadrant of the egg. For the formation of the organizer, we will study the role of the late blastula organizer in inducing the Spemann (gastrula) organizer, and the differentiation of the latter into anterior and posterior parts during gastrulation, using explants and molecular markers. We will also ask whether the entire spectrum of dorsalized- ventralized anatomies can be related quantitatively to one variable, the width (0 degrees - 360 degrees circumference) of the late blastula organizer. And finally for the functioning of the Spemann organizer itself, we will ask about the steps of planar induction of anteroposterior neural markers, the dependence of neural pattern on the age, size, and parts of the organizer, and the progressive acquisition of anterior fates by neural cells, again using explants and markers.
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