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不同的光感受器类型是如何在视网膜中被指定和定位的。果蝇眼是解决这个问题的一个有价值的模型系统。苍蝇眼是由数百个亚单位组成的复合体，称为小眼。在每个小眼内有不同的光感受器类型，小眼以不同的类别出现，包含不同的光感受器类型。光感受器类型因其视蛋白表达、轴突投射和在小眼内的位置而不同。我们在这里解决的主要问题是：(I)每个小眼内的光感受器是如何唯一指定的？(Ii)如何指明不同类型的小眼？ (1)R7感光器的特性：各小眼对紫外线敏感的感光器为R7细胞。来自分化的光感受器的信号接触假定的R7并激活细胞内的两个不同的细胞内信号-RAS和Notch(N)通路。我们希望了解这两条通路是如何相互作用来指定R7细胞的。它们是联合作用为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通路的激活是否允许RAS通路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，或者两条途径的整合。 (2)小眼内不对称性的规定：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。小眼对视网膜中的分级信息进行解码，以建立初始的不对称，然后将不对称信息传递给小眼的其他细胞。这里的问题是如何建立分级信息，以及如何对其进行解码并将其传达给该单元的所有单元。 (3)背缘的特点：背缘小眼是位于眼球后端的偏振光探测细胞，含有R7和R8细胞的特化。从邻近头部组织发出的信号仅在背部组织中诱发这些小眼。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.