TGF-β signaling is essential for the induction and patterning of the early embryonic germ layers. Within TGF-β signaling, regulation of BMP signaling is necessary for patterning the ectoderm, where ventrally located BMPs induce epidermis, and dorsally located BMP inhibitors allow for neural induction. In Xenopus laevis, this sensitivity of the ectoderm to BMP signaling allows for the differentiation of the presumptive ectoderm to be used as a readout of BMP activity. Increased BMP signaling expands epidermal tissue, and decreased BMP signaling results in an expansion of neural tissue. Tumor Necrosis Factor-Receptor Associated Factor 4 (TRAF4), is an adaptor protein with functions in ontogenic processes, adult epithelial progenitor cells and cancer metastasis. TRAF4 has been shown to potentiate BMP signaling, but the extent of TRAF4 involvement in the BMP pathway and the fate of the ectoderm are not well understood. In this study, I show that TRAF4 is needed for the differentiation of the epidermis and that TRAF4 is needed for robust BMP signaling to occur.
TRAF4 is expressed in the presumptive ectoderm of the early embryo, and enveloping ectoderm of the gastrula. At neurula stages, TRAF4 becomes restricted to dorso-anterior and neural tissue. TRAF4 knockdown in Xenopus laevis embryos results in incomplete gastrulation and a loss of anterior structures. Consistent with its expression pattern in the ectoderm, TRAF4 knockdown results in the loss of epidermal differentiation, and the ectoderm trends towards neural differentiation, suggesting that the presence of TRAF4 is needed for epidermal differentiation. In addition, embryos that overexpress BMP4 fail to gastrulate, yet knockdown of TRAF4 results in embryos that regain the ability to perform gastrulation movements. These data suggest that TRAF4 is positively regulating BMP signaling, and that TRAF4 is needed for proper gastrulation, and differentiation of the epidermis.
|Advisor:||Thomsen, Gerald H.|
|Commitee:||Gergen, J. Peter, Takemaru, Ken-Ichi, Talmage, David|
|School:||State University of New York at Stony Brook|
|Department:||Molecular and Cellular Pharmacology|
|School Location:||United States -- New York|
|Source:||DAI-B 77/02(E), Dissertation Abstracts International|
|Subjects:||Cellular biology, Developmental biology|
|Keywords:||BMP, Ectoderm, Epidermal differentiation, Neural differentiation, TGF-beta, TRAF4|
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