GENETIC HIERARCHY AND GENE FUNCTION IN VERTEBRATE EYES

描述（来自申请人摘要的逐字）：视力是关键性的 这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，但遗传学上的差异是显而易见的。 控制脊椎动物视网膜细胞分化的调节途径仍然存在， 不确定。此外，基因活性和细胞决定之间的联系 并没有得到很好的理解。该建议旨在研究细胞和 眼睛形成的分子机制：（1） 控制眼睛形成的不同基因之间的关系，然后（2） 描述了眼睛发育中两个视网膜基因Chx 10的作用 和小眼症通过分析眼睛的表情模式 在野生型胚胎和过度表达转录因子的胚胎中， 通过对单个基因的研究，我们可以勾勒出一个遗传层次。 显性负性抑制和增强子激活其功能， 发展中的动物将被用来更精确地定义功能 这些基因的关系。此外，过度表达或抑制 Chx 10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， 没有

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.