The Rockefeller University
1995 Searle Scholar
Patterning in Vertebrate Development
In my laboratory, we aim to elucidate the molecular mechanisms responsible for the formation and patterning of the vertebrate embryo. We plan to use two species of frogs for these studies, Xenopus laevis and Xenopus tropicalis. These amphibian embryos provide us with the opportunity to study development from the first cell cycle onward and to carry out experiments involving detailed manipulations of the embryos. We will focus our effort on providing a molecular answer to the following question: How is the nervous system formed? In vertebrates, this question is inherently linked to understanding the development of the dorsal axis. We will examine this problem at three levels. At the embryonic level, we will explore how the neuroectoderm is specified on the dorsal side. At the cellular level, we will work to determine what kind of cell-cell interactions mediate the transition to neural fate. Finally, at the molecular level, we will characterize molecular players involved in neural induction from the extracellular signals, their transduction within the cytoplasm, and their effect on transcriptional responses in the nucleus.
We have recently discovered that the inhibition of signals transduced through the activin pathway, a member of the TGF-_ family of growth factors, leads to the induction of the nervous system. Thus, we showed that activin antagonists can switch the fate of embryonic cells directly to a neural fate. Through this work, we have developed an assay system that will allow us to understand this mechanism in more detail. Also, we want to elucidate how the nervous system is patterned. We already know that activin antagonists induce anterior type (i.e., forebrain and midbrain) neural tissues in embryonic explants. We plan to use these explants to screen neurotrophic factors for their ability to modify the type of neural tissue induced in this assay system.
An important aspect of the work will be the development of new technologies for the study of the early embryos. We will continue to pioneer new techniques to improve our ability to study the vertebrate embryo. Among these, we aim to generate transgenic frogs and knockout strategies to evaluate the role of identified genes. Also, we will work to adapt recent advances in computer imaging to follow movements of individual cells in the whole living embryo.
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