Retina: The control of photoreceptor cell fate

描述（由申请人提供）：视网膜发育中的一个关键问题是如何指定不同的感光器类型并将其定位在视网膜内。果蝇的眼睛是解决这个问题的一个有价值的模型系统。蝇眼是由数百个称为小眼的亚单位组成的复合集合体。在每个小眼内有不同的感光细胞类型，小眼作为不同的类别出现，包含不同的感光细胞类型。不同类型的光感受器视蛋白的表达，轴突的投射，以及它们在小眼内的位置。我们在这里解决的主要问题是：（一）如何在每个小眼内的光感受器是唯一指定的？(ii)不同类型的小眼是如何区分的？ (1)R7光感受器的规格：每个小眼中的UV敏感光感受器是R7细胞。来自分化的光感受器的信号，其接触假定的R7并激活细胞内的两种不同的细胞内信号-Ras和Notch（N）途径。我们希望了解这两种途径如何相互作用以指定R7细胞。它们是以组合的方式为R7前体提供独特的发育线索，还是以不同的方式发挥作用？例如，N途径的激活是否允许Ras途径的激活而没有其他功能？一旦这些问题得到回答，我们将研究分子相互作用的性质，和/或两种途径的整合。 (2)小眼内的不对称性：每个小眼内的光感受器以不对称的方式排列，这与眼睛的光学特性密切相关。小眼解码视网膜中的分级信息，以建立初始的不对称性，然后将其传达给小眼的其他细胞。这里的问题是如何建立分级信息，以及如何将其解码并传达给单元的所有单元。 (3)背缘的特化：背缘小眼是在眼睛的背端发现的偏振光检测细胞，包含R7和R8细胞的特化。从邻近的头部组织发出的信号仅在背部组织中诱导这些小眼。我们希望了解来自头部组织的信号如何组织背缘小眼和其他相关的视网膜特化。

DESCRIPTION (provided by applicant): A critical question in retinal development is how different photoreceptor types are specified and positioned within a retina. The Drosophila eye is a valuable model system with which to address this question. The fly eye is a compound aggregate of many hundred sub-units called ommatidia. Within each ommatidium there are distinct photoreceptor types and ommatidia occur as different classes containing varying photoreceptor types. The photoreceptor types differ by their opsin expressions, their axonal projections, and their positions within the ommatidia. The major questions we are addressing here are: (i) how the photoreceptors within each ommatidium are uniquely specified? (ii) How the different types of ommatidia are specified? (1) Specification of the R7 photoreceptor: The UV sensitive photoreceptor in each ommatidium is the R7 cell. Signals from differentiating photoreceptors that contact the presumptive R7 and activate two distinct intracellular signals within the cell - the Ras and Notch (N) pathways. We wish to understand how these two pathways interact to specify the R7 cell. Do they act combinatorially to provide the R7 precursor with a unique developmental cue, or do they act in a different manner? For example could N pathway activation allow the activation of the Ras pathway and have no other function? Once these questions are answered we will examine the nature of the molecular interaction, and or integration of the two pathways. (2) Specification of asymmetry within the ommatidia: The photoreceptors in each ommatidium are arrayed in an asymmetric manner that is critically related to the optical properties of the eye. Ommatidia decode graded information in the retina to establish an initial asymmetry that is then communicated to the other cells of the ommatidium. The questions here are how the graded information is established, and how it is decoded and communicated to all cells of the unit. (3) The specification of the dorsal rim: The dorsal rim ommatidia are polarized light detector cells found in the dorsal extreme of the eye and contain specializations of the R7 and R8 cells. Signals emanating from the neighboring head tissue induce these ommatidia in only dorsal tissues. We wish to understand how signals from the head tissue organize the dorsal rim ommatidia and other associated retinal specializations.