Determination of Cone Photoreceptor Fate

光感受器(PR)是高度专门化的细胞，能将光能转化为有用的生理信号。 在脊椎动物中，睫状突、视杆和视锥启动视觉。杆和锥体的经典定义是 根据外节的形态，一个富含细胞膜的细胞器专门用于捕获 光及其处理，以便向其他视网膜神经元发出信号。PR在其上的光强度范围 操作也是它们定义的一个基本方面，杆状物在昏暗的光线下运行，圆锥体在较亮的光线下运行 灯。圆锥体启动我们的颜色和高敏锐度视觉，圆锥体进一步定义为波长敏感度 他们的眼球。尽管我们高度重视我们的视力，特别是我们的中等高度敏锐度的颜色 在视觉上，我们对锥体是如何在发育过程中产生的知之甚少。这些信息将有助于 当它们在多种导致失明的疾病中失效时，更换它们的努力。当前干细胞 方法在圆锥体生产中非常有限，主要是由于缺乏关于正常的 发育线索。这些方法需要新的策略来产生足够的锥体，使其成为 有效的治疗。 除了对治疗应用的好处外，对PR发生机制的了解 将有助于我们理解这类重要感觉神经元的进化和发展。 鉴于视觉的高价值，公关人员面临着沉重的选择压力。这导致了各种各样的 PR类型，使用经典定义的形态学和生理学模糊了杆状和圆锥体的定义。在……里面 此外，不同物种之间的杆状分布和不同类型的杆状突起有很大的差异。 视网膜上的视锥细胞。例如，在人类中，有一个小的高敏锐度区域，中央凹，在那里视锥细胞 唯一的公关类型。了解杆和锥体是如何确定的，将有助于理解 导致这些图案、形态和生理差异的一些机制 跨物种。 这笔赠款的重点将是锥体在发育过程中如何选择它们的命运的问题，利用 基因组数据和现代方法学。起点将是定义两个基因的转录调控 球果发生所需的关键基因OTX2和OC1，以及Notch1、Notch1控制的下游事件 已知最早的锥体发生调控因子，然后利用这些数据推导出锥体调控基因 网络(S)。

Photoreceptors (PRs) are highly specialized cells that transduce light energy into useful physiological signals. In vertebrates, the ciliary PRs, rods and cones, initiate vision. The classical definition of rods and cones is based upon the morphology of the outer segment, a membrane rich organelle specialized for the capture of light and its processing so as to signal other retinal neurons. The range of light intensities over which PRs operate is also a fundamental aspect of their definition, with rods operating in dim light and cones in brighter light. Cones initiate our color and high acuity vision, with cones further defined by the wavelength sensitivity of their opsin. Despite the high value we place on our vision, particularly our conemediated high acuity color vision, we know very little about how cones are generated during development. This information would aid in the efforts to replace them when they fail in many types of diseases leading to blindness. Current stem cell methods are very limited in cone production, principally due to a lack of knowledge regarding the normal developmental cues. New strategies are needed for these methods to produce enough cones to make this an effective therapy. In addition to the benefits for therapeutic applications, knowledge of the mechanisms of PR genesis would inform our understanding of the evolution and development of this important class of sensory neurons. Given the high value of vision, PRs are under heavy selective pressure. This has resulted in a wide variety of PR types, with a blurring of rod and cone definition using classically-defined morphology and physiology. In addition, there are dramatic differences among species in the distribution of rods and the different types of cones across the retina. For example, in humans, there is a small high acuity area, the fovea, where cones are the only PR type. An understanding of how rods and cones are determined would allow for an appreciation of some of the mechanisms that have driven these patterning, morphological, and physiological differences across species. The focus of this grant will be the question of how cones choose their fate during development, utilizing genomic data and modern methodologies. The starting point will be to define the transcription regulation of two key genes required for cone genesis, Otx2 and Oc1, and the downstream events under control of Notch1, the earliest known regulator of cone genesis, and then use these data to derive the cone gene regulatory network(s).