Function and Assembly of Basal Laminae During Nervous System Development

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Function and assembly of basement membranes in the nervous systemBasement membranes (BMs) are thin sheets of extracellular matrix that separate epithelial tissues from adjacent connective tissues. In the nervous system, they exist as the pial and the vascular BMs. Although it is well established that cells die when the BM they are attached to is defective, the role of the BM in neuronal survival is unclear. The experiments proposed in this project will address this important but understudied area of research. In addition, Dr. Halfter's laboratory will study how the BM is formed in the nervous system. His laboratory has worked out unique experimental procedures that dissolve and reconstitute the retinal BM in chick embryos by the sequential injections of collagenase and mouse laminin-1. The reconstitution of the BM, facilitated by laminin-1, can be blocked by antibodies to laminin-1, but not by antibodies to laminin-2. Both laminins differ only in the sequence of their alpha chains. Dr. Halfter's laboratory will localize the domain(s) of the laminin alpha 1 chain that is (are) critical in the assembly of a new BM. The successful outcome of the experiments would be the fist step in understanding the biochemical detail in building the multi-component BMs in vivo.