Ommatidial rotation and cell motility in the eye

描述(申请人提供)：视觉系统的功能是形成图像。由于视网膜中光感受器神经元的正确模式对于准确的视网膜原位轴突投射到视叶上是至关重要的，因此视网膜上皮内精确的光感受器排列是重要的。果蝇的视网膜是由数百个小眼或单位眼以及相关的光感受器神经元组成的立体图案。这种精确排列的建立为神经元光感受器细胞命运的诱导和构图提供了一个范例。这一过程需要EGF受体(EGFR)/RAS信号的第一次顺序波激活来诱导各自的神经元命运，同时需要FrizzledFZ/平面极性信号来正确地塑造光感受器神经元簇。最终光感受器构图和排列的一个有趣的方面是由一个称为小眼旋转的过程控制的。FZ信号在眼睛发育过程中调节旋转的方向，但旋转的实际执行需要不同的机制/途径。我们已经确定EGFR途径本身对旋转过程至关重要。有趣的是，下游效应级联不同于EGFR用于光感受器神经元诱导和存活的效应级联。本申请的范围是剖析光感受器运动和小眼旋转所需的特定的EGFR信号转导，并在此背景下确定EGFR和RAS下游所需的特定效应级联(S)。一组新发现的旋转特异性基因将与旋转特异性EGFR信号方面整合在一起。将结合果蝇的体内研究和生化实验来实现这一目标。EGFR的几个效应器已经从基因或分子上被鉴定出来，并将被分析它们在眼球旋转中的作用。EGFR/RAS信号也与多种形式的癌症有关，它的几个信号成分(如受体和RAS本身)是原癌基因。因此，在这一应用中获得的信息不仅将促进我们对视网膜细胞运动和模式的理解，而且对于癌症发生的研究也将是重要的。

DESCRIPTION (provided by applicant): The function of the visual system is to form images. As correct patterning of photoreceptor neurons in the retina is critical for the precise retinotopic axonal projections onto the optic lobes, precise photoreceptor arrangement within the retinal epithelium is important. The Drosophila retina is a stereo-typed pattern of several hundred ommatidia, or unit eyes, and the associated photoreceptor neurons. The establishment of this precise arrangement serves as a paradigm for neuronal photoreceptor cell fate induction and patterning. This process requires first sequential waves of EGF-receptor (Egfr)/Ras-signaling activation to induce the respective neuronal fates, simultaneously with Frizzled (Fz)/planar polarity signaling to pattern the photoreceptor neuron clusters correctly. An interesting aspect of the final photoreceptor patterning and arrangement is governed by a process called ommatidial rotation. Fz signaling regulates the direction of rotation during eye development, but a distinct mechanism/pathway is required for the actual execution of the rotation. We have identified the Egfr pathway as critical for the rotation process per se. Interestingly, the downstream effector cascade is distinct from the one used by Egfr for photoreceptor neuron induction and survival. The scope of this application is to dissect the specific Egfr signaling requirements for photoreceptor motility and ommatidial rotation, and to identify the specific effector cascade(s) required downstream of Egfr and Ras in this context. A set of newly identified rotation specific genes will be integrated with the rotation specific Egfr signaling aspects. A combination of Drosophila in vivo studies and biochemical experiments will be used to achieve this goal. Several effectors of Egfr have been identified genetically or molecularly and will be analyzed for their role in ommatidial rotation. Egfr/Ras signaling has also been implicated in many forms of cancer and several of its signaling components (e.g. the receptor and Ras themselves) are proto-oncogenes. Thus, the information acquired in this application will both advance our understanding of retinal cell motility and patterning, and will also be of importance for the study of carcinogenesis.