The role of wnt8 in posterior mesoderm formation
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The formation of vertebrate mesoderm relies on the integration of positional information provided by several intercellular signaling pathways, including the Wnt and Bone Morphogenic Protein (Bmp) pathways. Zygotic Wnt signaling has been shown in multiple vertebrate systems to perform two functions: to restrict the size of the dorsal mesoderm structure known as the organizer, and to promote the development of posterior mesoderm that populates the trunk and tail. Importantly, the organizer is a source of secreted Bmp antagonists that regulate Bmp-dependent ventral and posterior mesoderm patterning. Because the organizer impacts Bmp signaling activity, it is not clear whether functions attributed to zygotic Wnt signaling are in fact indirectly due to reduced Bmp activity. The objective of this thesis is to test the hypothesis that zygotic Wnt signaling plays two critical functions: to restrict the size of the organizer and to promote posterior mesoderm development in a Bmp-independent manner. To test this hypothesis, we characterized in depth the phenotypic defects of zebrafish embryos lacking Wnt8, the central ligand involved in zygotic Wnt-dependent mesoderm patterning. To identify Bmp-independent functions of Wnt8 signaling, we used double loss-of-function conditions to elevate Bmp signaling in embryos lacking Wnt8 function. Embryos were analyzed for the expression of a comprehensive set of mesoderm markers indicative of cell fates found in all spatial positions of the embryo. Our results show that, in addition to posterior mesoderm precursors being drastically reduced in Wnt8 morphants, anterior fates are disrupted as well. We found that increasing Bmp signaling largely has no effect on the Wnt8 morphant phenotype. However, slight rescue was observed in pronephric, heart tube, and vasculature precursors. We believe these results support the hypothesis that Wnt signaling maintains mesoderm progenitor cell populations, while Bmp signaling patterns mesoderm cell fates. Accordingly, Wnt8 signaling will appear to be epistatic to Bmp signaling during vertebrate axis patterning.
Kelton, Cathryn Renee (2008). The role of wnt8 in posterior mesoderm formation. Master's thesis, Texas A&M University. Available electronically from