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。由于视网膜中感光细胞神经元的正确图案化对于精确的视网膜定位轴突投射到视叶上是至关重要的，因此视网膜上皮内的精确感光细胞排列是重要的。果蝇的视网膜是由几百个小眼（或单位眼）和相关的感光神经元组成的刻板模式。这种精确排列的建立可以作为神经元感光细胞命运诱导和模式化的范例。该过程需要EGF受体（Egfr）/Ras信号传导激活的第一顺序波以诱导相应的神经元命运，同时卷曲（Fz）/平面极性信号传导以正确地图案化感光神经元簇。一个有趣的方面，最后的感光器图案和安排是由一个过程称为小眼旋转。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途径作为旋转过程本身的关键。有趣的是，下游效应级联与Egfr用于感光神经元诱导和存活的级联不同。本申请的范围是剖析光感受器运动和小眼旋转的特异性Egfr信号传导要求，并鉴定在此背景下Egfr和Ras下游所需的特异性效应级联。一组新鉴定的旋转特异性基因将与旋转特异性Egfr信号传导方面整合。果蝇体内研究和生物化学实验的结合将用于实现这一目标。已经确定了几个Egfr效应基因或分子，并将分析其在小眼旋转的作用。EGFR/Ras信号传导也涉及许多形式的癌症，并且其几种信号传导组分（例如受体和Ras本身）是原癌基因。因此，在此应用程序中获得的信息将促进我们对视网膜细胞运动和图案的理解，并且对于致癌作用的研究也具有重要意义。

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.