NEW NEURONS AND NEW SYNAPSES

这项建议是关于控制神经细胞的决心的 系统：是什么调节神经元和神经胶质细胞的种类和数量 制作的？新出现的共识是，血统不是最重要的 视网膜细胞增殖或分化的决定因素。一个 另一种假设是，细胞间的相互作用提供了重要的 允许的或有益的信号。所提出的模型系统采用了 研究是硬骨视网膜，之所以选择它，是因为它的数量有限 定义明确、高度有序的神经元类型，包括杆状和几个 在形态和分光光度上截然不同的锥体类型，它 具有较长的发育期和再生能力。这个 拟议的实验重点是细胞相互作用和位置线索 可能在控制细胞增殖和光感受器方面很重要 分化，尤其是非神经细胞(穆勒胶质细胞)的作用 和视网膜色素上皮)和分级决策策略 这可能会影响成为杆状还是锥状的选择。特定于细胞的 单抗和细胞特异性分子(酶、碳水化合物 部分等)将被用作承诺的标志和 分化和视网膜细胞的增殖、分化和 再生将在体内、幼虫和成年动物身上进行研究， 在分离的视网膜细胞的培养中 在体外进行重组。这些研究将提供有关 光感受器的发生，并可能揭示杆之间的重要差异 和锥体，这可能会导致对疾病过程的更好理解 以不同的方式影响视杆细胞(如视网膜退化和光- 损害)和其他涉及异常增殖的眼部病理 视网膜胶质细胞和/或视网膜色素上皮细胞(例如 糖尿病视网膜病变和增殖性玻璃体视网膜病变)。

This proposal is about the control of cell determination in the nervous system: what regulates the kinds and numbers of neurons and glial cells produced? The emerging consensus is that lineage is not the essential determinant of retinal cell proliferation or differentiation. An alternative hypothesis is that cell-cell interactions provide important permissive or instructive signals. The model system used n the proposed studies is the teleost retina, chosen because it has a limited number of well-defined, highly-ordered neuronal types, including rods and several morphologically and spectrophotometrically distinct cone types, and it has a prolonged developmental period and the capacity to regenerate. The proposed experiments focus on cell interactions and positional cues that might be important in controlling cell proliferation and photoreceptor differentiation, especially the role of non-neuronal cells (Muller glia and retinal pigmented epithelium) and hierarchical decision strategies that might influence the choice to become a rod or a cone. Cell-specific monoclonal antibodies and cell-specific molecules (enzymes, carbohydrate moieties, etc.) are to be used as markers of commitment and differentiation, and retinal cell proliferation, differentiation and regeneration will be studied both in vivo, in larvae and adult animals, and in cultures of dissociated retinal cells that are allowed to reaggregate in vitro. These studies will provide information about photoreceptor genesis, and may reveal important differences between rods and cones that might lead to a better understanding of disease processes that differentially affect rods (such as retinal degenerations and light- damage) and other ocular pathologies that involve abnormal proliferation of retinal glia and/or retinal pigmented epithelial cells (such as diabetic retinopathy and proliferative vitreoretinopathy).