Fundamental regulation of chordate heart development

描述（由申请人提供）： 这项研究计划的重点是阐明心脏发育的遗传学在原始的脊索动物玻璃海鞘。最初的努力将集中在脊椎动物Nkx 2.x基因家族Ci-Nkx的单一玻璃海鞘直系同源物的调节和功能上。通过电穿孔测试报告构建体的能力将允许快速鉴定控制Ci-Nkx表达的调控元件。该技术还将允许迅速鉴定这些元件内的功能上重要的结合位点。 将采用功能结合位点的鉴定来鉴定调节Nkx的因子。Ci-Nkx的错误表达和抑制将用于确定其功能意义并鉴定下游靶基因。 Nkx 2.5在脊椎动物心脏发育中的研究受到许多旁系同源物的阻碍。因此，分析玻璃海鞘Nkx的调控和功能可以为理解脊椎动物心脏遗传学的保守方面做出重大贡献。 对心脏遗传学的基本了解对于心脏相关疾病和出生缺陷的医学治疗的发展至关重要。

DESCRIPTION (provided by applicant): This research proposal focuses on elucidating heart developmental genetics in the primitive chordate Ciona intestinalis. Initial efforts will focus on the regulation and function of the single Ciona ortholog to the vertebrate Nkx 2.x gene family, Ci-Nkx. The ability to test reporter constructs through electroporation will allow rapid identification of the regulatory elements which control Ci-Nkx expression. This technique will also permit prompt identification of functionally important binding sites within these elements. Identification of functional binding sites will be employed to identify factors which regulate Nkx. Misexpression and repression of Ci-Nkx will be employed to determine its functional significance and to identify downstream target genes. Research on Nkx 2.5 in vertebrate heart development has been hindered by the presence of numerous paralogs. Therefore, analysis of Ciona Nkx regulation and function can make a significant contribution towards understanding conserved aspects of vertebrate heart genetics. A fundamental understanding of heart genetics is essential to the development of medical treatments for heart-related diseases and birth defects.