GENETIC HIERARCHY AND GENE FUNCTION IN VERTEBRATE EYES

描述(逐字摘自申请者的摘要)：视觉是关键的 取决于适当的眼睛形态和细胞类型的发育。 虽然许多与眼睛发育有关的基因已经被分离出来，但基因 控制脊椎动物视网膜细胞分化的调控途径仍然存在 未定。此外，基因活性和细胞决定之间的联系 还没有被很好地理解。这项提案旨在调查蜂窝和 眼球形成的分子机制：(1)确定功能性 控制眼睛形成的不同基因之间的关系，然后(2) 眼睛发育所必需的两个视网膜基因的作用特征 还有MITF或小眼炎。通过分析眼睛的表情模式 野生型胚胎和过度表达的胚胎中的转录因子 单独的基因，就有可能勾勒出一个遗传等级。 它们功能的显性-负性抑制和增强子激活 发育中的动物将被用来更准确地定义功能 这些基因之间的关系。此外，过度表达或抑制 Chx10和MITF在2-细胞期和胚胎视泡中(第18期) 可能揭示这些基因的新功能，这是之前在小鼠身上进行的研究 不。

DESCRIPTION (Verbatim from the applicant's abstract): Sight is critically dependent on the development of appropriate eye morphology and cell types. Although many genes involved in eye development have been isolated, the genetic regulatory pathways that control vertebrate retinal cell differentiation remain undetermined. Moreover, the link between gene activity and cell determination is not well understood. This proposal aims to investigate the cellular and molecular mechanisms of eye formation by (1) decifering the functional relationships among the different genes that control eye formation and then (2) characterizing the role of two retinal genes integral to eye development, Chx10 and Mitf or microphthalmia. By analyzing the expression patterns of the eye transcription factors in wild-type embryos and embryos over-expressing the individual genes, it will be possible to outline a genetic hierarchy. Dominant-negative inhibition and enhancer activation of their function in the developing animal will be used to more precisely define the functional relationships of these genes. In addition, over-expression or inhibition of Chx10 and Mitf at the 2-cell stage and in embryonic optic vesicles (stage 18) may reveal new functions for these genes that previous studies in mice have not.