The knowledge of the mechanisms of neurulation is essential for understanding the causes of various congenital brain defects. Although multiple factors may act in a concerned manner to shape the neuroepithelium into a tube, the principal driving forces for this process are now thought to originate from microfilaments of neuroepithelial cells. However, very little is known about the organization and functional activity of these microfilaments, especially in mammals. In view of this, a series of experiments employing light and electron microscopy and immunocytochemistry are proposed to gain a better understanding of the role of microfilaments in elevation and proper alignment of neural folds. We will use the mouse embryo as a model system and focus on (1) the relationship between the organization of microfilaments in neuroepithelial cells and bending of the neuroepithelium, (2) substructural features of apical microfilament bundles and their alterations during apical constriction of neuroepithelial cells and fusion of neural folds, and (3) localization of motility-related proteins relative to the organization of microfilaments in neuroepithelial cells. Information gained from the proposed study would provide (1) significant insights into the structural basis and molecular mechanisms of neural tube closure and (2) fundamental criteria for the analysis of abnormal cephalogenesis.
