Analysis Of Cell Fate Acquisition In the Retina

描述（由申请人提供）：脊椎动物视网膜由7种主要的细胞类型组成，以层状模式组织得非常精确。在胚胎发生过程中，所有视网膜神经元都是由形态学上一致的神经上皮细胞群产生的。在成熟视网膜中，单个神经元类别具有不同的功能、位置和形态。我们想确定是什么遗传机制赋予视网膜神经元和神经胶质这些独特的身份。

DESCRIPTION (provided by applicant): The vertebrate retina consists of seven major cell types organized with striking precision in a laminar pattern. During embryogenesis, all retinal neurons arise from a morphologically uniform population of neuroepithelial cells. In the mature retina, individual neuronal categories are characterized by distinct functions, positions, and morphologies. We would like to determine what genetic mechanisms confer these unique identities on the retinal neurons and glia. To identify the genetic loci involved in cell fate acquisition in the retina, we took a reverse genetic approach. Our collaborators and we took advantage of the extrauterine development and transparency of the zebrafish embryo to search for genes expressed in cell-class restricted patterns at the earliest stages of neuronal development in the retina. An in situ screen of over 7,000 clones revealed 9 that display these characteristics. The structure and function of these 9 genes will be characterized further. Structural characterization will reveal molecular motifs, such as protein-protein interaction interfaces, DNA binding domains, and catalytic sites providing insights into biochemical function. Functional characterization will take advantage of two techniques. First, we will use the recently introduced technique of gene knockdown to abolish function of individual genes. Second, we will express the genes under investigation in excess of the normal level. The phenotypic abnormalities produced by these experimental manipulations will reveal the roles these genes play in the development of the retina. As very few factors are known to be involved in early cell fate acquisition in the retina, these studies may provide key insights into this process. Characterization of cell-class restricted genes selected in a large-scale in situ hybridization screen described here will open a number of exciting research opportunities. Studies of their functions in higher vertebrates including humans may reveal relationships to human disorders such as photoreceptor dystrophies and glaucoma and may provide tools for the treatment of these disorders.