Goldowitz D, Rice D S, Williams R W
Center for Neuroscience, University of Tennessee, Memphis 38163, USA.
Prog Brain Res. 1996;108:3-15. doi: 10.1016/s0079-6123(08)62528-5.
The study of chimeric retinas has yielded insight on the early development of retina. The close match in chimerism ratios between right and left retinas is significant and supports the idea that both retinas originate from a common population of progenitors. We are able to estimate numbers of progenitor cells that contribute to the formation of the retina and the approximate time at which this small group is isolated from surrounding prosencephalic cell fields. These cells undergo at least five rounds of division before the first retinal neurons are generated. The mouse retina is not build from the center outward. There is simultaneous expansion and differentiation in all parts of the retina and as a result clones are not arranged in wedges. Instead the mouse retina is a patchwork of clones that do not differ greatly in size from center to periphery. The most consistent radial feature in mouse retina is a raphe left at the line of fusion of the margins of the ventral fissure. Processes that shape the clonal patchwork are both passive and active, intrinsic and extrinsic. Certain features of the clonal architecture of the retina, such as the size differences of clones are primarily passive responses to extrinsic forces on progenitor cells and their progeny. The fifteen-fold range in the size of cohorts is not due to intrinsic differences in the proliferative capacity of individual progenitor cells, but is due to the extent of cell movement and mixing at early stages of development. In contrast, active or intrinsic processes are illustrated by the partial (and still controversial) restriction of retinal progenitors, the possible clonal differences between ganglion cells with crossed and uncrossed projections, and the consistent differences in ratios of albino and pigmented genotypes in peripheral and central retina.
嵌合视网膜的研究为视网膜的早期发育提供了见解。左右视网膜嵌合率的紧密匹配意义重大,支持了两个视网膜均起源于共同祖细胞群体的观点。我们能够估计对视网膜形成有贡献的祖细胞数量,以及该小群体与周围前脑细胞区域分离的大致时间。这些细胞在产生第一批视网膜神经元之前至少经历五轮分裂。小鼠视网膜并非从中心向外构建。视网膜各部分同时进行扩张和分化,因此克隆并非呈楔形排列。相反,小鼠视网膜是由大小从中心到周边差异不大的克隆拼凑而成。小鼠视网膜中最一致的径向特征是在腹侧裂边缘融合线处留下的一条中缝。塑造克隆拼凑结构的过程既有被动的,也有主动的,既有内在的,也有外在的。视网膜克隆结构的某些特征,如克隆大小差异,主要是祖细胞及其后代对外在力量的被动反应。同组克隆大小的15倍差异并非由于单个祖细胞增殖能力的内在差异,而是由于发育早期细胞移动和混合的程度。相比之下,视网膜祖细胞的部分(仍有争议)限制、具有交叉和未交叉投射的神经节细胞之间可能存在的克隆差异,以及周边和中央视网膜中白化和色素沉着基因型比例的一致差异,都说明了主动或内在过程。