The long range goals of this project are to understand the molecular and cellular mechanisms underlying both CNS regionalization and the establishment of cell identity in the CNS. As a model system we have chosen to study the mammalian forebrain. Although the structure of forebrain is initially homogeneous, early in development it becomes regionalized, with the dorsal aspect giving rise to laminar cortical regions and the basal aspect giving rise to nuclear basal telencephalic regions. The initial part of this proposal is aimed at elucidating the cellular mechanisms underlying the process of regionalization. We have developed a new in vitro preparation, in order to study the movements of proliferating neural cells within the germinal zones of the forebrain during the period when the forebrain is becoming regionalized. This """"""""filet"""""""" preparation allows observation of the behavior of proliferating ventricular cells in intact developing cortex. These studies will examine the lateral dispersion of cells before, during, and after regionalization is occurring. Preliminary studies have revealed that while neural progenitors undergo lateral dispersion within the germinal zones of both the dorsal and basal aspects of forebrain, they do not cross the border region which divides them. The present study will further these findings by using both two dimensional and three dimensional video recordings to follow the movements of neural precursors within the different telencephalic germinal zones. Of particular interest will be: l) the coordination of lateral dispersion and the """"""""interkinetic"""""""" movements (which are associated with cell division); 2) examination of whether daughter cells show coordinated movement after cellular division; 3) the examination of the movements of the precursor cells in the border region where their lateral dispersion is restricted. In the second part of the proposal we will examine the mechanism by which """"""""segmental"""""""" borders restrict lateral dispersion and their significance in determining cell identity in the forebrain. This will be accomplished by performing in vitro and in vivo transplants of cells to heterotypic locations within embryonic telencephalon. By using a set of region specific cell markers to assess their identity we will be able to ask when during development cell identity is determined. Together the sets of experiments described in this proposal will examine the establishment of the subdivisions of forebrain and their significance to the determination of regional cell identity.
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