The long-term goal of this proposal is to make advances in our understanding of how signaling pathways and gene expression collaborate to control the earliest patterning events in the developing vertebrate embryo. Toward this end, we are combining molecular and embryological experiments to elucidate the mechanisms that control the formation of Spemann's organizer in the model organism Xenopus laevis. Spemann's organizer is a group of cells that collectively act as the central signaling center that establishes the vertebrate body plan by patterning the mesoderm and inducing neural tissue. The organizer influences the fate of surrounding cells by two mechanisms, the secretion of inducing proteins such as noggin and chordin and the regulation of morphogenesis and cell motility that involves direct cell-cell contacts. Therefore a defining molecular feature of organizer cells is the expression of specific signaling molecules such as chordin that help it perform its functions. In the absence of FGF signaling within the cells of the organizer, production of the ? inducing protein chordin is diminished, but the production of other organizer-specific molecules including noggin is not effected. In addition mesodermal patterning dictated by the organizer is disrupted, but the formation of most anterior neural structures in the embryo (head), which also require organizer function, is relatively normal. We hypothesize that FGF signaling within the organizer cells controls an important subset of the organizer's inducing functions at least in part through controlling organizer-specific transcription of chordin. We will address our view by examining the role(s) of FGF signaling pathway(s) within the organizer and the transcription of chordin as they relate to the ultimate inducing functions of Spemann's organizer. ? ?
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