Transcriptional Regulation In Early Embryonic Development

Abstract

Transcription factors are a class of proteins that function to regulate the expression of genes. During early development, their role is to provide the precise order of activation or suppression of genes that are required for the formation of an embryo. A major goal of a developing embryo is to establish a complete body plan that includes the development of all of the organ systems. Thus it is paramount that the correct genes are switched on or off to insure that all organ systems form.Our studies investigate the role of several transcription factors involved in coordinating the expression of genes that are essential for the development of skeletal muscle and blood vessels.In the formation of skeletal muscle, a class of transcription factors called the myogenic regulatory factors (MRFs) is known to promote the induction of the structural genes that comprise the skeletal muscle. In fact, the MRF family member, MyoD, has been termed the "master regulator" of skeletal muscle gene expression. However, a recently discovered transcription factor, MASTR, has been suggested to play a role in skeletal muscle development. Our studies of MASTR are the first to demonstrate that, in vivo, MASTR is necessary and sufficient to activate genes involved in the formation of skeletal muscle. Furthermore, MASTR cooperates with MRFs to induce skeletal muscle genes and therefore places MASTR among a group of transcription factors, such as the MRFs, that are essential regulators of skeletal muscle development.In vascular development, the Flk-1 gene is critical to the formation of blood vessels. Mice lacking Flk-1 do not produce angioblasts, the precursor cells that give rise to the endothelial cells that make up blood vessels. In our efforts to understand the regulation of this important vascular gene, we have discovered a new function of the Kruppel-like transcription factor 2 (KLF2) to activate Flk-1 expression. Moreover, we have identified a new Ets transcription factor (Etsrp) capable of inducing Flk-1 expression alone and in cooperation with KLF2. These findings uncover a novel mechanism by which KLF2 and Etsrp act to promote the expression of Flk-1 during embryonic vascular development.