Function and Assembly of Basal Laminae During Nervous System Development

神经系统基底膜的功能和组装基底膜(BMS)是一层薄薄的细胞外基质，将上皮组织与邻近的结缔组织隔开。在神经系统中，它们以软膜和血管BMS的形式存在。尽管众所周知，当细胞附着的BM有缺陷时，细胞就会死亡，但BM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未得到充分研究的领域。此外，哈夫特博士的实验室将研究BM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鼠层粘连蛋白-1来溶解和重建鸡胚胎中的视网膜BM。在层粘连蛋白-1的推动下，骨髓的重建可以被抗层粘连蛋白-1的抗体阻止，但不能被抗层粘连蛋白-2的抗体阻止。这两种层粘连蛋白的不同之处仅在于它们的阿尔法链的顺序。Halfter博士的实验室将定位层粘连蛋白α1链的结构域(S)，该结构域在组装新的BM时至关重要。实验的成功结果将是了解在体内建立多组分BMS的生化细节的第一步。

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.