Homeobox Gene Six3 in Forebrain and Visual System Development

描述(申请人提供)：前脑是中枢神经系统的最前部，在发育过程中起于端脑、间脑和眼睛。前脑的所有派生物都起源于前神经板。因此，破坏前脑发育的基因突变为剖析神经板区域化、建立命运限制和确定其所有主要衍生品的身份的机制提供了强大的工具。我们已经证明了Six3的限制表达模式具有功能相关性，因为它的活性对于脊椎动物的前脑、晶状体和视网膜的发育是必不可少的。这项建议的目的是继续系统地鉴定和表征Six3在前脑和视觉系统发育过程中的功能作用，作为帮助我们解开参与这些结构发生的细胞和分子机制的工具。在过去的几年里，我们产生了一系列无价的动物模型和分子工具，这些都是实现拟议目标的巨大财富。为此，我们建议继续使用Six3作为切入点，以更好地表征其在不同大脑结构发育和视网膜分化和分层中的功能作用。

DESCRIPTION (provided by applicant): The forebrain is the most anterior portion of the central nervous system and gives rises to the telencephalon, diencephalon, and the eyes during development. All derivatives of the forebrain originate from the anterior neural plate. Therefore, mutations in genes that disrupt forebrain development provide a powerful tool for dissecting the mechanisms that regionalize the neural plate, establish fate restrictions, and determine the identities of all its main derivatives. We have demonstrated that the restricted pattern of Six3 expression is of functional relevance as its activity is essential for vertebrate forebrain, lens and retina development. The goal of this proposal is to continue with the systematic identification and characterization of the functional roles of Six3 during forebrain and visual system development as a tool to help us unravel the cellular and molecular mechanisms participating in the genesis of these structures. During the last few years we have generated an invaluable collection of animal models and molecular tools that are a great asset in the accomplishment of the proposed goals. To this end, we propose to continue using Six3 as an entry point to better characterize its functional role in the development of different brain structures and retina differentiation and lamination.