Ommatidial rotation and cell motility in the eye

描述（由申请人提供）：视觉系统的功能是形成图像。由于视网膜中感光神经元的正确模式对于视网膜轴突向视叶的精确投影至关重要，因此视网膜上皮内感光神经元的精确排列非常重要。果蝇的视网膜是一个由几百个单眼和相关的感光神经元组成的固定模式。这种精确排列的建立为神经元感光细胞的命运诱导和模式提供了一个范例。这个过程需要egf受体(Egfr)/ ras信号激活的第一个连续波来诱导各自的神经元命运，同时卷曲(Fz)/平面极性信号来正确地塑造感光神经元簇。光感受器的最终模式和排列有一个有趣的方面，它是由一个叫做原轴旋转的过程控制的。Fz信号调节眼睛发育过程中的旋转方向，但旋转的实际执行需要不同的机制/途径。我们已经确定Egfr通路对旋转过程本身至关重要。有趣的是，下游效应级联与Egfr用于光感受器神经元诱导和存活的级联不同。本应用的范围是解剖光感受器运动和细胞旋转的特定Egfr信号要求，并确定在这种情况下Egfr和Ras下游所需的特定效应级联。一组新发现的旋转特异性基因将与旋转特异性Egfr信号传导方面相结合。将结合果蝇体内研究和生化实验来实现这一目标。Egfr的几个效应物已经被确定为基因或分子，并将分析它们在基质旋转中的作用。Egfr/Ras信号也与多种形式的癌症有关，它的一些信号成分（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将促进我们对视网膜细胞运动和模式的理解，也将对癌变的研究具有重要意义。

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.