McCaffery P, Lee M O, Wagner M A, Sladek N E, Dräger U C
Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
Development. 1992 Jun;115(2):371-82. doi: 10.1242/dev.115.2.371.
An aldehyde dehydrogenase present at high levels in the dorsal retina of the embryonic and adult mouse was identified as the isoform AHD-2 known to oxidize retinaldehyde to retinoic acid. Comparative estimates of retinoic acid levels with a reporter cell line placed the retinas among the richest tissues in the entire body of the early embryo; levels in ventral retina, however, exceeded dorsal levels. Retinoic acid synthesis from retinaldehyde in the dorsal pathway was less effective than the ventral pathway at low substrate levels and more effective at high levels. The dorsal pathway was preferentially inhibited by disulfiram, while ventral synthesis was preferentially inhibited by p-hydroxymercuribenzoate. When protein fractions separated by isoelectric focusing were analyzed for retinoic acid synthesizing capacity by a zymography-bioassay, most of the synthesis in dorsal retina was found to be mediated by AHD-2, and ventral synthesis was mediated by dehydrogenase activities distinct in charge from AHD-2. Postnatally, levels of highest retinoic acid synthesis shifted from ventral to dorsal retina. In the adult retina, the dorsal pathway persisted, but the preferential ventral pathway was no longer detectable. Our observations raise the possibility that retinoic acid plays a role in the determination and maintenance of the dorsoventral axis of the retina, and that the morphogenetically significant asymmetry here lies in the spatial arrangement of synthetic pathways.
在胚胎期和成年期小鼠的背侧视网膜中高水平存在的一种醛脱氢酶被鉴定为已知可将视黄醛氧化为视黄酸的AHD - 2同工型。利用报告细胞系对视黄酸水平进行的比较估计表明，在早期胚胎的整个身体中，视网膜是最富含视黄酸的组织之一；然而，腹侧视网膜中的视黄酸水平超过了背侧视网膜。在低底物水平时，背侧途径中从视黄醛合成视黄酸的效率低于腹侧途径，而在高底物水平时则更高。背侧途径优先受到双硫仑的抑制，而腹侧合成则优先受到对羟基汞苯甲酸的抑制。当通过等电聚焦分离的蛋白质组分通过酶谱 - 生物测定法分析视黄酸合成能力时，发现背侧视网膜中的大部分合成是由AHD - 2介导的，而腹侧合成是由电荷不同于AHD - 2的脱氢酶活性介导的。出生后，视黄酸合成最高水平从腹侧视网膜转移到背侧视网膜。在成年视网膜中，背侧途径持续存在，但优先的腹侧途径不再可检测到。我们的观察结果提出了一种可能性，即视黄酸在视网膜背腹轴的确定和维持中发挥作用，并且这里形态发生上显著的不对称性在于合成途径的空间排列。
