Perez R G, Halfter W
Department of Neurobiology, University of Pittsburgh School of Medicine, PA 15261.
Perspect Dev Neurobiol. 1994;2(1):75-87.
The large glycoprotein tenascin is one of the extracellular matrix proteins that is abundant in the developing nervous system. To determine its distribution and possible role in the ontogenty of the avian retinotectal system, the distribution of the protein, the expression of its mRNA, and the effect of the protein on growing retinal neurites in vitro was investigated. Immunocytochemistry demonstrated that relatively little tenascin was present in the optic fiber layer of the retina, the optic nerve and tract. Tenascin, however, was abundant in the stratum opticum of the tectum, the target of retinal axons in the brain. Whereas tenascin protein is found only in discrete portions and layers of the brain, in situ hybridization studies showed that tenascin mRNA was expressed throughout development by radial glial cells at the ventricular surfaces of the brain, distant from the tissue localization of the protein. Injection of antitenascin antiserum into the tectal ventricle disturbed the distribution of the protein in the tectum by binding tenascin closer to its origin at the ventricular border. This suggests that the localization of tenascin in the brain is not restricted to its site of synthesis, but is mediated by tenascin-binding proteins that are expressed in defined areas and layers in the brain. In vitro studies showed that tenascin did not promote neurite outgrowth of retinal axons. On the contrary, the addition of tenascin to retinal explants growing on collagen or on L1 slowed the growth rate of optic axons by as much as 50%. The inhibitory function in vitro suggests that this protein has a modulatory role in axonal growth in vivo. The absence of tenascin from the optic fiber layer of retina, optic nerve, and optic tract and its abundance in the tectum suggest that tenascin may function to slow the rapidly growing optic nerve fibers once they arrive at the tectum. The slowing of optic fiber outgrowth may then facilitate terminal arborization and synapse formation within the tectum. The abundant tenascin in synaptic layers may also serve to stabilize synapses once they have formed.
大糖蛋白腱生蛋白是发育中的神经系统中丰富的细胞外基质蛋白之一。为了确定其在鸟类视网膜顶盖系统个体发育中的分布及可能作用，研究了该蛋白的分布、其mRNA的表达以及该蛋白对体外培养的视网膜神经突生长的影响。免疫细胞化学显示，视网膜的视神经纤维层、视神经和视束中腱生蛋白相对较少。然而，腱生蛋白在顶盖的视层中含量丰富，视层是脑中视网膜轴突的靶区。虽然腱生蛋白仅在脑的离散部分和层中发现，但原位杂交研究表明，腱生蛋白mRNA在整个发育过程中由脑室表面的放射状胶质细胞表达，远离该蛋白的组织定位。将抗腱生蛋白抗血清注入顶盖脑室，通过将腱生蛋白结合在脑室边界附近更靠近其起源的位置，扰乱了该蛋白在顶盖中的分布。这表明腱生蛋白在脑中的定位不仅限于其合成部位，而是由在脑中特定区域和层中表达的腱生蛋白结合蛋白介导的。体外研究表明，腱生蛋白不促进视网膜轴突的神经突生长。相反，向在胶原蛋白或L1上生长的视网膜外植体中添加腱生蛋白，可使视神经轴突的生长速度减慢多达50%。体外的抑制功能表明该蛋白在体内轴突生长中具有调节作用。视网膜的视神经纤维层、视神经和视束中缺乏腱生蛋白，而顶盖中含量丰富，这表明腱生蛋白可能起到作用，一旦快速生长的视神经纤维到达顶盖，就减缓其生长速度。视神经纤维生长速度的减慢可能有助于在顶盖内形成终末分支和突触。突触层中丰富的腱生蛋白也可能在突触形成后起到稳定突触的作用。
