T-box Factor Regulation of Mesoderm Formation in the Mouse

University Of Pittsburgh, Pittsburgh PA

Investigators

Abstract

Gene expression is controlled by transcription factors, proteins that recognize and bind to specific sequences in the genome and facilitate the expression of target genes. This project focuses on how related transcription factors that share a common DNA binding domain and thus recognize similar DNA sequences regulate the expression of their targets when they are found in the same cells. One such example is the T-box transcription factors, T and Tbx6, which activate target gene expression during mesoderm formation in the mouse embryo. To understand how these related proteins coordinate gene expression to regulate cell fate decisions, transgenic approaches will be used to mis-express each of the proteins during mouse embryogenesis. Molecular and histological techniques will then be used to analyze the resulting embryos. While these proteins can recognize similar DNA sequences, whether they regulate similar target genes in the embryo is unknown. To identify T and Tbx6 target genes in embryonic tissues, biochemical assays will be used. Once targets are identified, transgenic embryos will be examined to determine how changes in the relative levels of T or Tbx6 affect target gene expression, thus linking target gene expression to embryonic consequences. Understanding how this T-box family coordinates target gene selection when they are found in the same cells will serve as a paradigm for other transcription factor families. These experiments will provide the PI, one graduate student and several undergraduates an opportunity to engage in research at a university that actively integrates research and teaching. Undergraduates have multiple opportunities to present their research, including science fairs and undergraduate research symposia. Examples from this research will be used for local K-12 outreach programs, including a middle school science club led by the PI.