Gilbert M, Smith J, Roskams A J, Auld V J
Department of Zoology, University of British Columbia, Vancouver, Canada.
Glia. 2001 May;34(3):151-64. doi: 10.1002/glia.1050.
The molecular mechanisms that drive glia-glial interactions and glia-neuronal interactions during the development of the nervous system are poorly understood. A number of membrane-bound cell adhesion molecules have been shown to play a role, although the precise nature of their involvement is unknown. One class of molecules with cell adhesive properties used in the nervous system is the serine-esterase-like family of transmembrane proteins. A member of this class, a glia-specific protein called gliotactin, has been shown to be necessary for the development of the glial sheath in the peripheral nervous system of Drosophila melanogaster. Gliotactin is essential for the development of septate junctions in the glial sheath of individual and neighboring glia. Mutations that remove this protein result in paralysis and eventually death due to a breakdown in the glial-based blood-nerve barrier. To study the role of gliotactin during vertebrate nervous system development, we have isolated a potential vertebrate gliotactin homologue from mice and rat and found that it corresponds to neuroligin 3. Using a combination of RT-PCR and immunohistochemistry, we have found that neuroligin 3 is expressed during the development of the nervous system in many classes of glia. In particular neuroligin 3 is expressed in the olfactory ensheathing glia, retinal astrocytes, Schwann cells, and spinal cord astrocytes in the developing embryo. This expression is developmentally controlled such that in postnatal and adult stages, neuroligin 3 continues to be expressed at high levels in the olfactory ensheathing glia, a highly plastic class of glia that retain many of their developmental characteristics throughout life.
在神经系统发育过程中驱动胶质细胞-胶质细胞相互作用和胶质细胞-神经元相互作用的分子机制目前还知之甚少。尽管一些膜结合细胞粘附分子的具体作用尚不清楚,但已证明它们发挥了一定作用。在神经系统中具有细胞粘附特性的一类分子是跨膜蛋白的丝氨酸酯酶样家族。该家族的一个成员,一种名为胶质触蛋白的胶质细胞特异性蛋白,已被证明对黑腹果蝇外周神经系统中胶质鞘的发育是必需的。胶质触蛋白对于单个胶质细胞和相邻胶质细胞的胶质鞘中分隔连接的形成至关重要。去除这种蛋白质的突变会导致瘫痪,并最终因基于胶质细胞的血神经屏障的破坏而死亡。为了研究胶质触蛋白在脊椎动物神经系统发育过程中的作用,我们从小鼠和大鼠中分离出了一种潜在的脊椎动物胶质触蛋白同源物,发现它对应于神经连接蛋白3。通过逆转录聚合酶链反应(RT-PCR)和免疫组织化学相结合的方法,我们发现神经连接蛋白3在许多类型的胶质细胞的神经系统发育过程中表达。特别是在发育中的胚胎的嗅鞘胶质细胞、视网膜星形胶质细胞、雪旺细胞和脊髓星形胶质细胞中表达神经连接蛋白3。这种表达受到发育调控,使得在出生后和成年阶段,神经连接蛋白3在嗅鞘胶质细胞中继续高水平表达,嗅鞘胶质细胞是一类高度可塑性的胶质细胞,在整个生命过程中保留了许多其发育特征。