Function and Assembly of Basal Laminae During Nervous System Development

基底膜（basal membrane, BMs）是将上皮组织与邻近结缔组织分开的细胞外基质薄片。在神经系统中，它们以基底细胞和血管脑转移瘤的形式存在。虽然已经确定，当细胞所附着的基底膜有缺陷时，细胞会死亡，但基底膜在神经元存活中的作用尚不清楚。本项目中提出的实验将解决这一重要但研究不足的研究领域。此外，哈夫特博士的实验室将研究脑脊髓瘤是如何在神经系统中形成的。他的实验室已经制定出独特的实验程序，通过连续注射胶原酶和小鼠层粘连蛋白-1来溶解和重建鸡胚胎中的视网膜基质。由层粘连蛋白-1促进的BM的重建可以被层粘连蛋白-1抗体阻断，但不能被层粘连蛋白-2抗体阻断。两种层粘连蛋白仅在α链的序列上有所不同。Halfter博士的实验室将定位层粘连蛋白α 1链的结构域，这对新BM的组装至关重要。该实验的成功结果将是了解构建多组分脑转移瘤的生物化学细节的第一步。

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.