Trevor Thomas, Undergraduate Researcher

Alaska Heart Institute Fellow

"Role of Williams Syndrome Transcription Factor in Xenopus laevis"

Abstract:  Williams Syndrome (WS) is a genetic disorder that results in cardiovascular defects and visual/spatial processing deficits. One of several genes absent in WS patients is Williams Syndrome Trascription Factor (WSTF). WSTF interacts with Imitation Switch (ISWI) to form the WSTF-ISWI Chromatin Remodeling Complex (WICH), an ATP-dependent chromatin remodeling complex that is conserved in vertebrate species. When WSTF expression is inhibited in vivo in Xenpus laevis embryos, the WICH complex is destabilized, and the resulting embryos exhibit defects in development of the brain and eye.  We have begun to investigate the effects of WICH complex depletion on two key genes involved in neural development: bone morphogenic protein 4 (Bmp4) and Sonic Hedgehog (Shh). Bmp4 antagonizes neural development, and its levels are reduced during early neurulation in normal Xenopus embryos, though Bmp4 is later required during development of the eye. In contrast, Shh is essential for development of neural tissues. Shh levels in whole embryos decrease in the absence of either WSTF or ISWI, and Bmp4 levels increase in the absence of ISWI. However, both Bmp4 and Shh are expressed in precise spatial patterns in developing embryos, and it is not known whether depletion of WSTF or ISWI changes the patterns of expression of these genes. I will use in situ hybridization to map the spatial and temporal expression of Bmp4 and Shh in embryos lacking WSTF. I will also test whether specific conserved regions of the WSTF protein are required for normal expression of Bmp4 and Shh.