Gerhardt H, Rascher G, Schuck J, Weigold U, Redies C, Wolburg H
Institute of Pathology, University of Tübingen, Tübingen, Germany.
Glia. 2000 Aug;31(2):131-43.
Glial cells play a crucial role in the organization and function of the nervous system. Cell-cell adhesion receptors of the cadherin family have been shown to participate in distinct morphogenetic processes throughout the development of the CNS, but little is known about glial expression of cadherins. Applying immunofluorescence and confocal laser scanning microscopy, we investigated R- and B-cadherin expression in relation to the glial cell differentiation in the optic nerve head and pecten oculi of developing chicken. Throughout embryonic development, R- and B-cadherin were expressed in distinct cell populations, which differentiated into distinct subtypes of glial cells. R-cadherin was located in the glia limitans perivascularis et superficialis of the optic nerve and in cells bordering the optic nerve head, where it comes in contact with the retina. B-cadherin was located in the glia limitans perivascularis et superficialis of the pecten oculi and in a subset of cells at the retinal border. R-cadherin-expressing cells differentiated unequivocally into a glial fibrillary acidic protein (GFAP)-positive but glutamine synthetase (GS)-negative phenotype, whereas B-cadherin-expressing glia developed into a GS-positive but GFAP-negative phenotype. In addition, the B-cadherin-positive population developed into a highly pigmented cell type, which was consistently associated with pecten-type capillaries. By contrast, the R-cadherin-positive glia remained unpigmented and surrounded normal brain-phenotype capillaries. These data suggest that glial cells, like neurons, may use the expression of different cadherins to segregate and differentiate into distinct subtypes, which goes hand in hand with their involvement in special functions and morphogenetic processes. To address this issue, we selectively lysed both glial subtypes in developing embryos by microinjection of R- and B-cadherin antibodies with complement. First evidence is presented for R-cadherin-positive glial cells as crucial to the organization of the optic nerve and axonal guidance at its lateral margin. B-cadherin-positive cells are involved in the axonal guidance at the pecteneal margin, avoiding the ingrowth of axons into the pecten.
神经胶质细胞在神经系统的组织和功能中发挥着关键作用。钙黏蛋白家族的细胞间黏附受体已被证明参与中枢神经系统发育过程中不同的形态发生过程，但关于钙黏蛋白在神经胶质细胞中的表达情况却知之甚少。我们应用免疫荧光和共聚焦激光扫描显微镜技术，研究了发育中的鸡视神经乳头和栉膜中R-钙黏蛋白和B-钙黏蛋白的表达与神经胶质细胞分化的关系。在整个胚胎发育过程中，R-钙黏蛋白和B-钙黏蛋白在不同的细胞群体中表达，这些细胞群体分化为不同亚型的神经胶质细胞。R-钙黏蛋白位于视神经的血管周围和表面神经胶质界膜以及与视神经乳头相邻且与视网膜接触的细胞中。B-钙黏蛋白位于栉膜的血管周围和表面神经胶质界膜以及视网膜边缘的一部分细胞中。表达R-钙黏蛋白的细胞明确分化为胶质纤维酸性蛋白（GFAP）阳性但谷氨酰胺合成酶（GS）阴性的表型，而表达B-钙黏蛋白的神经胶质细胞则发育为GS阳性但GFAP阴性的表型。此外，表达B-钙黏蛋白的细胞群体发育为一种高度色素沉着的细胞类型，这种细胞始终与栉膜型毛细血管相关。相比之下，表达R-钙黏蛋白的神经胶质细胞仍无色素沉着，并围绕着正常脑表型的毛细血管。这些数据表明，神经胶质细胞与神经元一样，可能利用不同钙黏蛋白的表达来分离并分化为不同的亚型，这与其参与特殊功能和形态发生过程密切相关。为了解决这个问题，我们通过显微注射R-钙黏蛋白和B-钙黏蛋白抗体与补体，选择性地裂解发育胚胎中的两种神经胶质细胞亚型。首次有证据表明，表达R-钙黏蛋白的神经胶质细胞对视神经的组织及其外侧边缘的轴突导向至关重要。表达B-钙黏蛋白的细胞参与栉膜边缘的轴突导向，避免轴突长入栉膜。
