Elvin Brown, Ph.D.

Thesis abstract:

A central question in the study of vertebrate development is how to account for the exquisite interplay of genes within differentiating cells and of groups of cells as they create the body plan and organ systems of the vertebrate embryo. It has become clear that gene regulation by epigenetic processes adds a formerly unappreciated level of complexity to the regulatory network of development. One form of epigenetic gene regulation is embodied in ATP-dependent chromatin remodeling complexes, which use the energy of ATP hydrolysis to alter the interactions of DNA and histones. Chromatin remodeling complexes can both promote and repress expression of a gene at the appropriate time and place in vertebrate development. The list of their known roles in development is long and growing. Here I have studied the developmental role of CHRAC17, a subunit of the CHRAC and ATAC complexes, by visualizing its expression and by ablating CHRAC17 function in Xenopus laevis embryos. Whole mount in situ hybridization localizes CHRAC17 expression to the neural tube, cranial placodes, and myotomes. Loss of CHRAC17 function following injection of embryos with CHRAC17-specific morpholino oligonucleotides results in abnormal development in the neural tube, eyes, notochord, and pharyngeal pouches, underlining the critical importance of CHRAC17 function in Xenopus development. Similarly, ablating the function of CHD4, the ATPase motor of the NuRD chromatin remodeling complex, resulted in severe developmental abnormalities in early Xenopus development.