The neural tube gives rise to the brain and spinal cord. The neural tube forms when a flat sheet of cells curls up and seals together. The surface ectoderm (SE) surrounds the folding neural tube and is required for the two sides of the tube to meet and close properly and ultimately for the neural tissue to be covered by an epithelial barrier. Failure to properly close and cover the neural tube results in neural tube defects including exencephaly and spina bifida. Neural tube defects are a common class of birth defects and can severely impact quality of life. In the cranial region, the SE reaches over the physical gap between the closing neural folds and then seals over the closing neural tube in a zippering fashion. Closing epithelial sheets often have actin cables that surround the site of closure and direct migration. Preliminary evidence from the Niswander lab suggests that the SE also has strong actin-rich cables at the leading edge. My research project aims to test the hypothesis that actin cables in the SE are regulated by the RhoA pathway to allow epithelial cells to reach over a gap to close the neural tube. My objectives are to determine how the actin cables close the SE and what proteins regulate actin cable formation and function in the SE. Characterization of actin cable function in the mouse embryo SE will be accomplished through time lapse microscopy and transgenic mice. Regulators of the RhoA pathway will be identified through cellular studies using a micropatterned in-vitro assay and CRISPR technology of a cultured human cell line. The long term goals of this research are to understand how neural tube closure is accomplished and to identify molecular mechanisms involved in neural tube closure. This research program will provide new insights into the function of the SE in neural tube closure and will identify the roles of some factors involved in the process. Outcomes of this research may facilitate the prevention and repair of neural tube defects.
