Regulation of Neuronal Proliferation and Differentiation

描述（由申请人提供）：这些项目的总体长期目标 研究是为了更好地了解不同类型的视网膜病变 神经元在视网膜发育过程中产生。十多年前，我们开始 研究来确定视网膜细胞类型的多样性是如何在 组织发生的过程我们用视网膜作为模型系统来开发 神经元多样性产生的原则，可以适用于 中枢神经系统。在过去的十年里，我们的研究和 其他人的研究表明，单个细胞的命运来自于相互作用， 在细胞微环境和内在的转录 在细胞中表达的调节剂。虽然我们已经从这个原则中得到了 各种视网膜细胞类型的研究，它是无处更好地证明比 在锥体光感受器的发展中，在这个应用中，我们有 我决定把我们的努力集中在了解多样性是如何产生的 在这个特定的细胞类别中。尽管这些研究涉及一个基本的 发展神经生物学的特征，因为它们将导致更好的 在视锥光感受器中的基因表达的表征，他们还将 提供的信息，可能证明有用的治疗退行性疾病 视网膜疾病，如黄斑变性。除了可能 识别对视锥光感受器生物学重要的新基因， 了解将视网膜细胞导向特定命运的因素， 在开发视网膜修复的合理疗法方面也至关重要 使用视网膜干细胞。

DESCRIPTION (provided by applicant): The overall long term objective of these studies is to provide a better understanding of how different types of retinal neurons are generated during retinal development. Over ten years ago, we began studies to determine how the diversity of retinal cell types comes about during the process of histogenesis. We used retina as a model system to develop principles for the generation of neuronal diversity that could apply to the central nervous system in general. Over the past ten years, our studies and those of other have shown that individual cell fates arise from an interplay between the cellular microenvironment and the intrinsic transcriptional regulators expressed in a cell. While we have derived this principle from studies of various retinal cell types, it is nowhere better demonstrated than in the development of the cone photoreceptors, and in this application we have decided to focus our efforts to the understanding of how diversity is generated within this specific cell class. Although these studies address a fundamental feature of developmental neurobiology, since they will result in a better characterization of gene expression in cone photoreceptors, they will also provide information that may prove useful for the treatment of degenerative retinal disorders, such as macular degeneration. In addition to potentially identifying new genes important for cone photoreceptor biology, a better understanding of the factors that direct retinal cells to specific fates will also be critical in developing rational therapies for repair of the retina using retinal stem cells.