Our long-term goal is to understand the signals that pattern the early vertebrate embryo. We study this problem predominantly in the frog Xenopus laevis. This animal produces large numbers of eggs that are readily manipulated by injection and microsurgery. The combination of experimental embryology and molecular manipulation provide the tools to understand embryonic signaling at the molecular level. Many of the paradigms for early developmental mechanisms in vertebrates have come from work with amphibians, and many of the signaling activities that bring about early developmental decisions in vertebrates have been identified first in amphibians. During previous grant periods, we have identified signals that act in early axis formation, mesoderm patterning and neural induction. In conjunction with the work of many other groups, this has led to a coherent picture of how the embryonic axes are established, and how a cascade of signal transductions leads to the elaborate pattern of the gastrula. Despite the progress that has been made in understanding embryonic signals, there is still only a partial picture of how the detailed pattern of the embryo emerges. The intracellular mediation of signaling is poorly understood, and although the main pathways that signal in development have been identified, the precise roles and modulation of these pathways remains to be determined. The formation of the neural plate with its elaborate patterning in both anterior-posterior and mediolateral axes poses a particular challenge, and this proposal will examine the integration of signaling pathways that induce and pattern the neural plate. Particular focus will be given to Fibroblast Growth Factor signaling in neural patterning, and in neural crest formation. The integration of signals that induce the neural crest will be studied by exploiting and comparing various manipulations that bring about neural crest development. ? ? ?
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