Functions of early B cell factor in xenopus neuronal and muscle development

The development of an animal from a single cell to an organism requires that individual cells undergo several sequential processes. The final stages, termed commitment and differentiation, rely heavily on the cell-intrinsic activity of regulatory transcription factor networks. The early B cell factor (EBF) family transcription factors are known to have an important influence on commitment and differentiation in neurons, B cells and adipocytes in vertebrate animals, and muscle cells in invertebrate animals. The full range of their activity, though, is not understood. We have utilized a microarray screen in Xenopus laevis to identify an extensive list of candidate targets of EBF transcriptional activity, as a step toward expanding understanding of the scope of EBF functions. This thesis focuses on the functions of EBF proteins in neuron and muscle cell development. To expand current knowledge of EBF functions in neuronal development, we selectively chose candidate targets from the microarray screen that have expected function in neurons, and verified that their expression depends on EBF activity. These targets demonstrate several previously unknown functions of EBF proteins in neuronal cell commitment and differentiation. We also have discovered a new function of the EBF protein partner ZFP423 as a synergistic mediator of the critical Notch signaling pathway, and show that EBF proteins can promote neuronal commitment in part by blocking the function of ZFP423. We next demonstrate that EBF proteins are necessary for normal Xenopus skeletal muscle development, and that they act by controlling expression of several genes critical for commitment and differentiation of muscle cells. This thesis significantly contributes to understanding of the function of EBF proteins in neuronal development. It also demonstrates for the first time an important role for EBF proteins in muscle cell development in vertebrates. Overall, this thesis expands our understanding of how EBF proteins participate in the complex transcriptional regulation of vertebrate development.