One of the fundamental aspects of vertebrate embryonic development is the transformation of a spherical or disc-shaped embryo into an elongated body with a head at one end and a tail at the other. Movements of individual cells within the tissues of the early embryo cause the overall narrowing and extension of the body axis, separating the head from the tail with an elongated spinal cord. How these cell movements are organized and coordinated is not known, and this is a critical question to be answered, as failure of body axis elongation can lead to severe malformations or death of the embryo. The proposed studies will address this question in mouse embryos, using mice that carry mutations in specific genes that lead to defects in body axis elongation and spinal cord formation. The effects of these mutations on cell movements in the neural tube and notochord, two tissues that contribute to the formation of the spinal cord, will be determined using time-lapse imaging of mutant and normal embryos. Changes at the subcellular and molecular level within the cells of the neural tube and notochord that affect body axis elongation will be examined using protein biochemistry and immunohistochemistry. In addition, the relative contribution of cell behavior within individual tissues (neural tube, notochord, somitic mesoderm) to overall body axis elongation will be examined using genetic approaches to target mutations to those specific tissues. These studies will provide significant new understanding of the cellular and molecular mechanisms regulating body axis formation, as well as novel insights into the general regulation of complex tissue movements during development. This project will have broader impacts in several ways. On the scientific level it will identify the key elements of body axis elongation and clarify how genetic and environmental factors may influence embryonic development. On the educational front, it will provide opportunities for both undergraduate and graduate students, particularly those from under-represented groups, to participate in research, and will provide materials for educational use at all levels (high school, undergraduate, graduate).
