Altshuler D, Lo Turco J J, Rush J, Cepko C
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Development. 1993 Dec;119(4):1317-28. doi: 10.1242/dev.119.4.1317.
The retina offers a model system for investigating the mechanisms that control cell type determination and differentiation in the vertebrate central nervous system. Previously, rod photoreceptor development in vitro was found to require a diffusible activity released by retinal cells (D. Altshuler and C. Cepko, Development 114, 947-957, 1992). In this report, we show that retinal-cell-conditioned medium and extracts contain two separable activities that influence rod development: a > 10 kDa inhibitory activity, and a stimulatory activity that is < 1 kDa and heat stable. Taurine was found to be a component of the < 1 kDa fraction and to stimulate rod development when added to retinal cultures. Taurine was not the only rod-promoting factor in these retinal preparations, however, as conditioned medium and extracts stimulated a higher level of rod development than did taurine alone. Taurine uptake into cells could be blocked without inhibiting taurine's ability to stimulate rod development, arguing against an osmoregulatory or nutritive mechanism of action. Finally, a competitive antagonist of taurine's bioactivity was identified and shown partially to inhibit rod development in retinal explants, suggesting that taurine may normally act to stimulate rod development in the retina. These results provide evidence for three activities, one of which is taurine, that are candidate regulators of rod photoreceptor development in vivo.
视网膜为研究脊椎动物中枢神经系统中控制细胞类型确定和分化的机制提供了一个模型系统。此前发现,体外视杆光感受器的发育需要视网膜细胞释放的一种可扩散活性物质(D. 阿尔特舒勒和C. 塞普科,《发育》114卷,947 - 957页,1992年)。在本报告中,我们表明视网膜细胞条件培养基和提取物含有两种可分离的影响视杆发育的活性物质:一种分子量大于10 kDa的抑制活性物质,以及一种分子量小于1 kDa且热稳定的刺激活性物质。发现牛磺酸是分子量小于1 kDa部分的一种成分,添加到视网膜培养物中时可刺激视杆发育。然而,牛磺酸并非这些视网膜制剂中唯一促进视杆发育的因子,因为条件培养基和提取物比单独的牛磺酸能刺激更高水平的视杆发育。牛磺酸进入细胞的过程可被阻断,而不影响其刺激视杆发育的能力,这表明其作用机制并非渗透调节或营养机制。最后,鉴定出一种牛磺酸生物活性的竞争性拮抗剂,并表明其可部分抑制视网膜外植体中的视杆发育,这表明牛磺酸可能通常在视网膜中起到刺激视杆发育的作用。这些结果为三种活性物质提供了证据,其中一种是牛磺酸,它们是体内视杆光感受器发育的候选调节因子。