The mammalian secondary palate is formed from two wedge- shaped masses of tissue, the palatal shelves, that initially grow down vertically from the maxillary processes to occupy positions on either side of the tongue. Subsequently, the shelves undergo a reorientation to a horizontal positon above the tongue wheree they meet in the midline, adhere and fuse to one another to form the normal secondary palate. Failure of this reorientiation leads to cleft palate. The long-term goal of this research is to identify the activities and interrelationships of the secondary palatal shelves' components which are responsible for their reorientation. Two specific regions of the shelf's epithelial perimeter have been shown to have altered cell form and to increase in cell density during the course of reorientation. This increase is not attributable to cell division. Changes in epithelial architecture require changes in the underlying basement membrane.
The specific aims of this project are to: 1) Characterize the temporal and spatial distribution of the major components of the basement membrane, the basal epithalial cel surface and the sublaminar mesenchymal region of active and inactive epithelial segments prior to and during palatal shelf reorientation; and 2) Determine if regional differences in the turnover of glycosaminoglycans and collagen occur at the basement membrane prior to and during shelf reorientation which correlate with the localized epithelial cell behaviors observed during reorientation. Two major techniques will be used to achieve these specific aims: 1) light and electron microscopic immunolabeling with antibodies specific to basement membrane components; and 2) isotopic pulse labeling visualized by autoradiography to follow the turnover of basement membrane components in these regions. These studies will provide basic information regarding which basement membrane components are associated with the changes in epithelial cell density accompanying shelf reorientation. These data will permit us to better target future studies on the role of certain molecules in shelf reorientation. Ultimately, detailed knowledge of the activities and interrelationships of the palatal shelf components which are responsible for shelf closure should allow predictions of agents, circumstances and gestations times of exposure which are likely to produce cleft palate.
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