Dysraphic defects of the central nervous system are among the most common congenital anomalies present in newborn humans. The proposed project will examine formation of the neural tube, the rudiment of the adult central nervous system, focusing on mechanisms involved in bending of the neural plate. Chicken embryos will be used as models to study this process. Five major questions will be addressed: (1) Are the neural folds pulled or pushed toward the dorsal midline? (2) What roles do changes in cell shape play in the shaping and bending of the neural plate? (3) How do changes in neuroepithelial cell shape occur? (4) Do localized changes in cell shape depend upon interactions with adjacent tissues or are they independent of such interactions? and (5) What specific changes occur in the sizes and shapes of flask-and spindle-shaped neuroepithelial cells. By addressing these questions with the experimental methodology proposed herein (i.e., laser and conventional microsurgery, tissue transplantation, whole embryo culture, light and electron microscopy, morphometrics, stereology, immunocytochemistry, histochemistry, autoradiography, and drug treatment), the mechanisms that are normally involved in formation of the neural tube will be better defined and insight should be gained into how this process may go awry, leading to certain serious congenital anomalies.
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