When the vertebrate nervous system first appears in the embryo, it is a flat sheet of neuroepithelium that shapes itself into a neural plate, then rolls into a tube. Failure of these processes produces some of the most frequent birth defects found in human infants. The object of this research is to examine the role of the boundary with the epidermis at the edge of the neural plate, and the role of the boundary between neural plate and notoplate (a domain of cells at the plate midline) in shaping the neural plate and rolling it into a tube. The cortical tractor model offers an explanation for the mechanics of neurulation that involves these two boundaries as lies that organize the otherwise random movements of the cells in the plane of the sheet. These hypotheses will be directly tested by implanting, for example, a piece of notoplate from an embryo that has been labelled with lineage tracers into the notoplate of an unlabelled host embryo then following the behavior of the labelled cells to see whether they behave as predicted. The model predicts that the cells will move about randomly amongst the unlabelled cells of the host notoplate, and when some of the cells encounter the neural plate/notoplate boundary, they will remain there. This forceful intercalation of cells along the boundary is hypothesized to be the force that elongates the midline of the neural plate. Similar predictions apply to neural plate cells on the other side of the boundary, and implants of labelled neural plate pieces will test that. The donor cells will be labelled with fluorescent dextran markers that remain in each cell, and they will be visualized in frontal sections by fluorescent microscopy. Some living culture of the neural plate will also be observed by time-lapse video with flashes of UV light to follow the actual movements of the labelled cells. Similar studies will be make at the more complex epidermis/neural plate boundary. In this case the mode predicts that neural plate cells will attempt to crawl beneath the epidermis, raising it into a fold, and epidermis will also try to crawl beneath the neural plate. Implanted labelled cells will be examined in three dimensional reconstructions from serial sections using computer morphometrics. Scanning electron microscopy of fractured specimens will also be used. The topology at this boundary is too complex to determine what the cells are doing by ordinary techniques. The cortical tractor model predicts that cells at the edge of the neural plate, at the boundary with the epidermis, will crawl beneath the epidermis until they loose themselves from the neuroepithelium. These cells should then be part of the neural crest cells. The epidermis may also contribute to the neural crest. Whether this is true should be revealed by following the behavior and ultimate positions of labelled cells. These methods will either confirm the model that has been proposed, or negate it so other explanations will be needed. In the latter case, the information form these experiments should help construct a new model to explain neurulation. The above experiments will be done in amphibian embryos because neurulation in them has been best analyzed, and they are most amenable to the necessary microsurgery and labelling with lineage tracers. However, it is proposed also to test the proposition that both epidermis and neural plate contribute to the neural crest by doing quail/chick transplants and using the quail nucleolar marker to trace the implanted quail cells.
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