INDUCTION AND COMPENTENCE IN THE RETINA

谱系研究表明，视网膜细胞以及许多其他细胞 在脊椎动物的神经系统中，生来就有多能文化研究 已经证明了细胞间的相互作用可以驱动这些多能性 细胞走向特定的命运。这是一项调查 这些感应通路的性质。对于非洲爪哇的光感受器，有 两个在时间上截然不同的归纳事件。第一个是必须转弯的 在视杆细胞和视锥细胞中表达的某些抗原，以及第二种 诱导细胞表达杆状特异标记物。两种通用的解决方案 决心与这些独立的诱因是一致的。一举成名 单个细胞暴露于一系列诱导性事件，这些事件越来越多 限制它的命运；在另一种情况下，单一的不同的相互作用导致 不同的细胞类型。这项提案的一个目的是区分 通过使用混合细胞培养的组合来实现这两种可能性 和免疫细胞化学标记。这项提议的另一个主要目标是 明确测试类似的归纳方案是否用于其他 视网膜中的细胞类型。在进化上有一种保守的秩序 脊椎动物的视网膜组织发生，我们将研究 发生这种情况的可能性是因为感应信号在 特定的序列，或者是因为细胞改变了它们的反应能力 到感应信号。能力的变化将通过删除 视网膜不同发育阶段的标记细胞，暴露在 他们对相同的归纳线索，并检查外观 标记细胞中的特定细胞类型。这次会议的最后一个主要目标是 建议研究特定的生长因子在视网膜中的作用 体内发育，通过显性激活和显性- 体内生长因子受体阴性形式，并检查视网膜 免疫组织化学方法检测细胞发育。 这项建议的长期目标是了解 脊椎动物神经系统中细胞和细胞的决定 分子水平。人们必须了解谁诱导了谁，什么信号 以及受体是什么。这项建议为更好的发展铺平了道路 对神经系统中细胞发生的顺序的理解 特别是用于产生有组织的细胞的工作模型 由特定的归纳事件序列产生的复杂性。视网膜是一种 脊椎动物中枢神经的高度可及和研究得很好的部分 该系统将很好地作为未来工作的试验性系统 这一类。 对视网膜中细胞是如何决定的基本了解，以及 在培养和体内控制这些诱导事件的能力， 可能对手术或损伤后的视网膜再生有影响。 这项工作在理解胚胎方面也可能有应用。 视网膜畸形。

Lineage studies have shown that retinal cells, as well as many other cells in the vertebrate nervous system, are born pluripotent Culture studies have demonstrated that cellular interactions can drive these pluripotent cells toward particular fates. This is a proposal to investigate the nature of these inductive pathways. For Xenopus photoreceptors, there are two temporally distinct inductive events. The first is necessary to turn on some antigens expressed in both rods and cones, and the second one induces cells to express rod specific markers. Two general schemes of determination are consistent with these separate inductions. In one a single cell is exposed to a series of inductive events that increasingly restrict its fate; in the other, single distinct interactions induce the different cell types. One aim of this proposal is to distinguish between these two possibilities by a using a combination of mixed cell cultures and immunocytochemical tagging. Another main objective of this proposal is to test explicitly whether similar inductive schemes are used for other cell types in the retina. There is an evolutionarily conserved order in retinal histogenesis in vertebrates, and we will investigate the possibilities that this occurs because inductive signals arise in a particular sequence, or because cells change their competence to respond to inductive signals. Changes in competence will be assayed by removing labeled cells from the retina at different stages of development, exposing them to the same inductive cues, and examining the appearance of particular cell types among the labeled cells. The last major goal of this proposal is to examine the role of particular growth factors in retinal development in vivo, by misexpression of dominant-activated and dominant- negative forms of growth factor receptors m vivo, and examining retinal cell development immunohistochemically. The long term objectives of this proposal are to understand the cascade of cell determination in the vertebrate nervous system at a cellular and a molecular level. One has to understand who induces who, what the signals are, and what the receptors are. This proposal paves the way for a better understanding of the order of cellular genesis in the nervous system, in particular a working model for the generation of organized cellular complexity from a specific sequence of inductive events. The retina is a highly accessible and well studied part of the vertebrate central nervous system and will serve well as an experimental system for future work of this sort. The basic understanding of how cells are determined in the retina, and the capability of controlling these inductive events in culture and in vivo, may have implications for retinal regeneration after surgery or injury. This work may also have applications in understanding the embryonic malformations of the retina.