Rapaport D H, Patheal S L, Harris W A
Division of Anatomy, Department of Surgery, University of California San Diego, La Jolla, CA 92093-0604, USA.
J Neurobiol. 2001 Nov 5;49(2):129-41. doi: 10.1002/neu.1070.
Factors in the environment appear to be responsible for inducing many of the cell fates in the retina, including, for example, photoreceptors. Further, there is a conserved order of histogenesis in the vertebrate retina, suggesting that a temporal mechanism interacts in the control of cellular determination. The temporal mechanism involved could result from different inducing signals being released at different times. Alternatively, the inducing signals might be present at many stages, but an autonomous clock could regulate the competence of cells to respond to them. To differentiate between these mechanisms, cells from young embryonic retinas were dissociated and grown together with those from older embryos, and the timing of photoreceptor determination assayed. Young cells appeared uninfluenced by older cells, expressing photoreceptor markers on the same time schedule as when cultured alone. A similar result was obtained when the heterochronic mixing was done in vivo by grafting a small plug of optic vesicle from younger embryos into older hosts. Even the graft cells at the immediate margin of the transplant failed to express photoreceptor markers earlier than normal, despite their being in contact with older, strongly expressing host cells. We conclude that retinal progenitors intrinsically acquire the ability to respond to photoreceptor-inducing cues by a mechanism that runs on a cell autonomous schedule, and that the conserved order of histogenesis is based in part on this competence clock.
环境因素似乎是诱导视网膜中许多细胞命运的原因,包括例如光感受器。此外,脊椎动物视网膜存在保守的组织发生顺序,这表明一种时间机制在细胞命运决定的控制中相互作用。所涉及的时间机制可能是由于在不同时间释放不同的诱导信号。或者,诱导信号可能在许多阶段都存在,但一个自主时钟可以调节细胞对它们作出反应的能力。为了区分这些机制,将来自年轻胚胎视网膜的细胞解离,并与来自较老胚胎的细胞一起培养,然后检测光感受器决定的时间。年轻细胞似乎不受较老细胞的影响,与单独培养时一样在相同的时间表达光感受器标记物。当通过将来自较年轻胚胎的一小片视泡移植到较老宿主中在体内进行异时混合时,也得到了类似的结果。即使移植边缘的移植细胞也没有比正常情况更早地表达光感受器标记物,尽管它们与强烈表达的较老宿主细胞接触。我们得出结论,视网膜祖细胞通过一种按细胞自主时间表运行的机制内在地获得了对光感受器诱导信号作出反应的能力,并且组织发生的保守顺序部分基于这种能力时钟。