Dysraphic defects of the central nervous system are among the most common and serious congenital anomalies present in newborn humans. The proposed project will examine the mechanisms acting in the process of neurulation, the formation of the neural tube; the latter structure constitutes the rudiment of the entire adult central nervous system. Avian embryos developing in vitro will be used as model systems to study neurulation. The proposed project has three specific aims: 1) to construct prospective fate maps of the avian blastoderm at stages preceding formation of the definitive neural plate, to examine the relative (and perhaps spatially and temporally coordinated) movements of cells in the three germ layers throughout neurulation, and to determine when in development, fate and behavior become irrevocably fixed for cell populations having preeminent roles in formation and patterning of the neuraxis; 2) to ascertain the relative functions of several important cell behaviors and crucial developmental events in neurulation by conducting a medley of strategic experiments; and 3) to examine possible tissue interactions underlying the neuraxial pattern formation that occurs during (and soon after) closure of the neural groove and formation of the neural tube, as assessed by alterations in the spatial and temporal expression of protein products of selected candidate positional identity genes. Several techniques will be used to accomplish these aims (e.g., methods of experimental embryology, including microinjection, microsurgery, and construction of quail/chick transplantation chimeras; light and electron microscopy; timelapse videomicroscopy; specific chemical inhibition procedures; immunocytochemistry; fluorescent cell labeling; statistical analyses of changes in morphological features, especially in relation to cell division; whole embryo culture). Through accomplishing these aims, the mechanisms that are normally involved in formation of the neural tube will be better defined and insight will be gained into how this process may go awry and lead to devastating congenital anomalies.