HOMEOBOX GENE SIX3 IN EYE DEVELOPMENT

描述(改编自申请人的摘要)：申请人克隆了 同源异型盒基因Six3在鱼类胚胎中过度表达时，导致 异位晶状体形成。这显然激励了申请者继续 该基因进一步被认为是脊椎动物胚胎眼睛中非常重要的基因 发展。该提案的目标是了解Six3的作用 在脊椎动物眼睛发育过程中的作用并阐明调控途径 参与了这一过程。申请者已经制作了具有 Six3基因通过胚胎干细胞方法失活。这项提议是 进一步研究这些小鼠。申请人已经至少证明了 SIX3的一些监管要素，并建议研究 脊椎动物和苍蝇之间这些元素的进化保守。 大鼠前神经板Six3表达的调控分子 视泡也将被识别使用表征的调节 筛选小鼠E8.0-8.5前神经板的探针元件 表达式库。受Six3监管的目标将通过以下方式揭示 野生型cDNA在Six3-/前神经中的消减 板/眼野胚胎区。参与调控的新基因 在眼睛发育的过程中将被确定为 从表达Six3的细胞中特异地获得的cDNA文库 E8.0-8.5小鼠胚胎的前神经板和视野。这些 实验将进一步定义参与的机制和途径 脊椎动物的眼睛发育，应该及早识别新的控制基因 这一过程的步骤。因此，它们将增进我们对 与眼睛相关的出生缺陷。

DESCRIPTION (Adapted from applicant's abstract): The applicant cloned a homeobox gene called Six3 which, when overexpressed in fish embryos, causes ectopic lens formation. This has obviously inspired the applicant to pursue this gene further as one which is very important in embryonic vertebrate eye development. The goal of the proposal is to understand the role of Six3 during vertebrate eye development and to elucidate the regulatory pathways involved in the process. The applicant has already made mice which have the Six3 gene inactivated via embryonic stem cell methods. The proposal is to study these mice further. The applicant has already identified at least some of the regulatory elements of Six3 and proposes to study the evolutionary conservation of these elements between vertebrates and flies. The molecules that control Six3 expression in the anterior neural plate in optic vesicles will also be identified using the characterized regulatory elements as probes to screen a mouse E8.0-8.5 anterior neural plate expression library. Targets regulated by Six3 will be revealed by subtraction of cDNAs prepared from wild type in Six3-/anterior neural plate/eye field embryonic regions. Novel regulatory genes that participate in the process of eye development will be identified by the construction of a cDNA library specifically derived from the Six3 expressing cells in the anterior neural plate and eye field of E8.0-8.5 mouse embryos. These experiments will further define the mechanisms and pathways involved in vertebrate eye development and should identify novel genes controlling early steps of this process. Thus, they will enhance our understanding of eye-related birth defects.