Date of Degree

9-2017

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biology

Advisor(s)

Daniel Weinstein

Committee Members

Cathy Savage Dunn

Alicia Melendez

Carmen Melendez Vasquez

Gerald H Thomsen

Subject Categories

Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Developmental Biology | Molecular Genetics | Other Cell and Developmental Biology

Keywords

Development, T-box proteins, Cancer, Germ layers, Pluripotency

Abstract

All of the tissues in triploblastic organisms, with the exception of the germ cells, arise from the three germ layers, ectoderm, mesoderm and the endoderm. The identification of the genes that underlie the differentiation of these layers is crucial to our understanding of development. T-box family proteins are DNA-binding transcriptional regulators that play important roles during germ layer formation in the early vertebrate embryo. Well-characterized members of this family, including the transcriptional activators Brachyury and VegT, are essential for the proper formation of mesoderm and endoderm, respectively. To date, T-box proteins have not been shown to play a role in the promotion of the third primary germ layer, ectoderm. In this study, we have identified two T-box proteins, Tbx2 and Tbx3, as important players in the development of the vertebrate embryo with majority of our work focused on Tbx2. Our studies indicate that the T-box factor Tbx2 is both sufficient and necessary for ectodermal differentiation in the frog Xenopus laevis. Tbx2 is expressed zygotically in the presumptive ectoderm, during blastula and gastrula stages. Ectopic expression of Tbx2 represses mesoderm and endoderm, while loss of Tbx2 leads to inappropriate expression of mesoderm- and endoderm-specific genes in the region fated to give rise to ectoderm. Misexpression of Tbx2 also promotes neural tissue in animal cap explants, suggesting that Tbx2 plays a role in both the establishment of ectodermal fate and its dorsoventral patterning. Our studies demonstrate that Tbx2 functions as a transcriptional repressor during germ layer formation, and suggest that this activity is mediated in part through repression of target genes that are stimulated, in the mesendoderm, by activating T-box proteins.

In addition to Tbx2, we also identified Tbx3, another T-box transcription factor, whose expression begins early in development. Our data indicate that Tbx3 is expressed in the animal pole of Xenopus laevis embryos, where it functions to repress mesodermal and endodermal genes. Taken together, our results point to a critical role for T-box proteins in limiting the potency of blastula-stage progenitor cells during vertebrate germ layer differentiation.

 
 

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