Patterning of the Primitive Heart Tube in Zebrafish

斑马鱼原始心管的模式

• 批准号: 7762730
• 负责人: JAU-NIAN CHEN
• 金额: $ 37.2万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762730
• 关键词: Address; Affect; Animal Model; Ankyrins; Architecture; Bilateral; Binding; Biochemical; Biological Process; Cardiac; Cardiac Myocytes; Cell Proliferation; Cell Shape; Critical Pathways; Cultured Cells; Cytoskeleton; DNA Sequence Rearrangement; Data; Defect; Development; Developmental Process; Embryo; Embryonic Heart; Event; Genes; Genetic; Genetic Screening; Goals; Growth; Health; Heart; Hour; Human; Lead; Lesion; Life; Mind; Molecular; Molecular Genetics; Morphogenesis; Mutation; Myocardial; N-terminal; Na(+)-K(+)-Exchanging ATPase; Nature; Pattern; Phenotype; Process; Processed Genes; Proteins; Reporting; Research Personnel; Riots; Role; Signal Transduction; Site; Structure; Time; Tissues; Tube; Tubular formation; Vertebrates; Zebrafish; cardiogenesis; clinically relevant; embryonic cell culture; gene function; insight; loss of function; mutant; positional cloning; research study; success

DESCRIPTION (provided by applicant): Abnormalities in the formation and/or function of the embryonic heart often lead to embryonic lethality or severe health problems later in life. Understanding the fundamental mechanisms underlying early heart development at the cellular and molecular level is not only scientifically challenging but is also clinically relevant. We choose the zebrafish as our model organism to study early cardiac patterning because it is amenable to genetic, embryological and molecular manipulation. Furthermore, the embryonic hearts of all vertebrate species undergo similar morphogenic processes and are regulated by conserved genetic circuits. Information obtained from one model organism may apply to other vertebrates, including humans. In this project, we take three independent approaches to study the cellular and molecular mechanisms governing primitive heart tube morphogenesis. Our recent study on the zebrafish heart and mind mutation uncovered an unexpected role of Na,K-ATPase a1B1 in the elongation of the primitive heart tube. We will investigate the impact of loss of function of Na,K-ATPase a1 B1 on the cellular architecture of cardiomyocytes. We will also investigate the interaction of Na,K-ATPase a1 B1 other genes critical for the morphogenesis of the primitive heart tube in zebrafish at the cellular and genetic level (Aim 1). Furthermore we will investigate the molecular mechanism by which the Na,K-ATPase a1 B1 regulates the elongation of the primitive heart tube in the zebrafish and in cultured cells, as the first step toward understanding genetic networks involved in the primitive heart tube formation (Specific Aim 2). Finally, from an ongoing zebrafish genetic screen, we identified a new mutation affecting the patterning of the primitive heart tube. We will characterize the phenotypes of this mutant and identify the molecular lesion causing this mutant phenotype (Aim 3). The combination of cellular, molecular and genetic studies proposed in this project will provide new and in-depth insight into mechanisms of primitive heart tube morphogenesis.

描述（由申请人提供）：胚胎心脏的形成和/或功能异常通常会导致胚胎死亡或生命后期的严重健康问题。在细胞和分子水平上了解早期心脏发育的基本机制不仅具有科学挑战性，而且具有临床意义。我们选择斑马鱼作为研究早期心脏模式的模型生物，因为它适合遗传、胚胎学和分子操作。此外，所有脊椎动物的胚胎心脏都经历相似的形态发生过程，并受到保守的遗传电路的调节。从一种模式生物获得的信息可能适用于其他脊椎动物，包括人类。在这个项目中，我们采用三种独立的方法来研究控制原始心管形态发生的细胞和分子机制。我们最近对斑马鱼心脏和思维突变的研究发现了 Na,K-ATPase a1B1 在原始心管伸长中的意外作用。我们将研究 Na,K-ATPase a1 B1 功能丧失对心肌细胞结构的影响。我们还将在细胞和基因水平上研究 Na,K-ATPase a1 B1 其他基因对斑马鱼原始心管形态发生至关重要的相互作用（目标 1）。此外，我们将研究 Na,K-ATPase a1 B1 调节斑马鱼和培养细胞中原始心管伸长的分子机制，作为了解参与原始心管形成的遗传网络的第一步（具体目标 2）。最后，从正在进行的斑马鱼基因筛查中，我们发现了一种影响原始心管模式的新突变。我们将表征该突变体的表型，并确定导致该突变体表型的分子损伤（目标 3）。该项目提出的细胞、分子和遗传学研究的结合将为原始心管形态发生机制提供新的、深入的见解。

项目成果

Regulation of Sufu activity by p66β and Mycbp provides new insight into vertebrate Hedgehog signaling.

• DOI: 10.1101/gad.249425.114
• 发表时间: 2014-11-15
• 期刊: Genes & development
• 影响因子: 10.5
• 作者: Lin C;Yao E;Wang K;Nozawa Y;Shimizu H;Johnson JR;Chen JN;Krogan NJ;Chuang PT
• 通讯作者: Chuang PT

Mutation in utp15 disrupts vascular patterning in a p53-dependent manner in zebrafish embryos.

• DOI: 10.1371/journal.pone.0025013
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Mouillesseaux K;Chen JN
• 通讯作者: Chen JN

The PAF1 complex component Leo1 is essential for cardiac and neural crest development in zebrafish.

• DOI: 10.1016/j.ydbio.2010.02.020
• 发表时间: 2010-05-01
• 期刊: DEVELOPMENTAL BIOLOGY
• 影响因子: 2.7
• 作者: Nguyen, Catherine T.;Langenbacher, Adam;Hsieh, Michael;Chen, Jau-Nian
• 通讯作者: Chen, Jau-Nian

Calcium signaling: a common thread in vertebrate left-right axis development.

• DOI: 10.1002/dvdy.21704
• 发表时间: 2008-12
• 期刊: DEVELOPMENTAL DYNAMICS
• 影响因子: 2.5
• 作者: Langenbacher, Adam;Chen, Jau-Nian
• 通讯作者: Chen, Jau-Nian

Zebrafish as a model for cardiovascular development and disease.

斑马鱼作为心血管发育和疾病的模型。

• DOI: 10.1016/j.ddmod.2009.02.003
• 发表时间: 2008
• 期刊: Drug discovery today. Disease models
• 作者: Nguyen,CatherineT;Lu,Qing;Wang,Yibin;Chen,Jau-Nian
• 通讯作者: Chen,Jau-Nian