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（由申请人提供）：先天性心脏病是一些最常见的出生缺陷。为了了解这些缺陷的本质，研究信号传导途径非常重要，例如正常心脏发育所需的视黄酸 (RA) 信号传导。 RA 信号传导对于成体和胚胎组织的细胞分化很重要。成人组织中 RA 信号传导的缺失会导致癌症，而胚胎中的 RA 信号传导缺失会导致发育缺陷。过多的 RA 信号传导也可能致畸。因此，RA 信号传导水平的调节对于正确的细胞分化很重要。 Yelon 最近利用斑马鱼发现了 RA 信号在适当的心肌祖细胞选择中的新作用。如果没有 RA 信号传导，太多的心肌祖细胞会在离散区域内分化。影响心肌细胞祖细胞选择的分子机制尚未得到研究。此外，我们不知道是什么在调节 RA 信号传导。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) 并确定 RA 信号传导的新型调节剂。