The goal of the experiments to be described in this proposal is to elucidate the cellular and molecular events underlying the induction of the floor plate by the notochord. The floor plate is a specialized set of neuroepithelial cells located at the ventral midline of the embryonic spinal cord. The floor plate appears to be responsible for the differentiation and organization of neurons within the ventral spinal cord and, at later stages of development, plays a pivotal role in the guidance of axons within the spinal cord. We have previously shown that the differentiation of functional and antigenic properties that are specific to the floor plate is dependent on an inductive signal from the underlying notochord. The experiments described here use a simple assay system to measure the induction of floor plate-specific gene expression in cells of the lateral neural plate that would not normally give rise to floor plate. This assay will be used to examine the developmental expression pattern and biochemical properties of the notochord-derived signal and as a detection method in the identification of the activity. We will use an expression cloning approach to identify cDNAs that encode the floor plate-inducing activity. In the longer term, the goal is to understand the mechanisms by which neuroepithelial cells respond to the notochordal signal and initiate a program of floor plate differentiation. The identification of a notochord-derived floor plate-inducing signal and the elucidation of its mechanisms of action will be an important step in the understanding of early inductive processes and in the differentiation and organization of the early neural tube.
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