Retinoic Acid Signaling and Cardiac Cell Differentiation

视黄酸信号传导和心肌细胞分化

• 批准号: 7054595
• 负责人: Joshua Waxman
• 金额: $ 4.6万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054595
• 关键词: animal genetic material tag; biological signal transduction; cardiac myocytes; cardiogenesis; cell differentiation; cell growth regulation; congenital heart disorder; developmental genetics; gene expression; gene mutation; genetic screening; genetically modified animals; molecular biology; nuclear receptors; postdoctoral investigator; reporter genes; retinoate; retinoid binding proteins; stem cells; transfection /expression vector; vertebrate embryology; zebrafish

DESCRIPTION (provided by applicant): Congenital heart defects are some of the most common birth defects. To understand the nature of these defects it is important to study signaling pathways, like Retinoic Acid (RA) signaling, which is required for normal heart development. RA signaling is important for cell differentiation in adult and embryonic tissues. Loss of RA signaling in adult tissues can lead to cancer and in embryos leads to developmental defects. Too much RA signaling can also be teratogenic. Thus, modulation of RA signaling levels is important for proper cell differentiation. The Yelon, using zebrafish, recently discovered a new role for RA signaling in proper cardiomyocyte progenitor selection. Without RA signaling, too many cardiomyocyte progenitors differentiate within a discrete area. The molecular mechanisms that influence cardiomyocyte progenitor selection have not been investigated. Moreover, we are unaware of what is regulating RA signaling. Therefore, the specific aims of my post-doctoral research are: 1) to determine how RA signaling levels affect differentiation of cardiomyocyte progenitors in zebrafish; 2) to determine which RA receptors regulate cardiomyocyte progenitors differentiation; 3) and to identify novel regulators of RA signaling.

描述(申请人提供)：先天性心脏缺陷是最常见的出生缺陷之一。为了了解这些缺陷的本质，重要的是研究信号通路，如维甲酸(RA)信号，这是正常心脏发育所必需的。RA信号在成体和胚胎组织的细胞分化中起重要作用。在成人组织中，RA信号的缺失会导致癌症，而在胚胎中，RA信号的缺失会导致发育缺陷。过多的RA信号也可能导致畸形。因此，RA信号水平的调节对于适当的细胞分化是重要的。Yelon使用斑马鱼，最近发现了RA信号在正确的心肌祖细胞选择中的一个新角色。在没有RA信号的情况下，太多的心肌祖细胞在一个离散的区域内分化。影响心肌祖细胞选择的分子机制尚未被研究。此外，我们不知道是什么在调节RA信号。因此，我博士后研究的具体目标是：1)确定RA信号水平如何影响斑马鱼心肌祖细胞的分化；2)确定哪些RA受体调节心肌祖细胞分化；3)寻找RA信号的新调节因子。