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. ? ?

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Cell Development and Function Integrated Review Group (CDF)
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Klein, Steven
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University of Wisconsin Madison
Schools of Medicine
United States
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Reid, Christine D; Zhang, Yan; Sheets, Michael D et al. (2012) Transcriptional integration of Wnt and Nodal pathways in establishment of the Spemann organizer. Dev Biol 368:231-41
Sheets, M D; Fritz, B; Hartley, R S et al. (2010) Polyribosome analysis for investigating mRNA translation in Xenopus oocytes, eggs and embryos. Methods 51:152-6
McGivern, Jered V; Swaney, Danielle L; Coon, Joshua J et al. (2009) Toward defining the phosphoproteome of Xenopus laevis embryos. Dev Dyn 238:1433-43
Zhang, Yan; Sheets, Michael D (2009) Analyses of zebrafish and Xenopus oocyte maturation reveal conserved and diverged features of translational regulation of maternal cyclin B1 mRNA. BMC Dev Biol 9:7
Lund, Elsebet; Liu, Mingzhu; Hartley, Rebecca S et al. (2009) Deadenylation of maternal mRNAs mediated by miR-427 in Xenopus laevis embryos. RNA 15:2351-63
Zhang, Yan; Forinash, Kara D; McGivern, Jered et al. (2009) Spatially restricted translation of the xCR1 mRNA in Xenopus embryos. Mol Cell Biol 29:3791-802
Song, Jikui; McGivern, Jered V; Nichols, Karl W et al. (2008) Structural basis for RNA recognition by a type II poly(A)-binding protein. Proc Natl Acad Sci U S A 105:15317-22
Mitchell, Tracy; Jones, Elizabeth A; Weeks, Daniel L et al. (2007) Chordin affects pronephros development in Xenopus embryos by anteriorizing presomitic mesoderm. Dev Dyn 236:251-61
Lane, Mary Constance; Sheets, Michael D (2006) Heading in a new direction: implications of the revised fate map for understanding Xenopus laevis development. Dev Biol 296:12-28
Constance Lane, Mary; Davidson, Lance; Sheets, Michael D (2004) BMP antagonism by Spemann's organizer regulates rostral-caudal fate of mesoderm. Dev Biol 275:356-74

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