Retinoic Acid Signaling and Cardiac Cell Differentiation

描述（由申请人提供）：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信号在成人和胚胎组织的细胞分化中起重要作用。成人组织中RA信号的缺失可导致癌症，胚胎中RA信号的缺失可导致发育缺陷。过多的类风湿性关节炎信号也可能是致畸的。因此，RA信号水平的调节对于正常的细胞分化是重要的。使用斑马鱼的Yelon最近发现RA信号在适当的心肌细胞祖细胞选择中的新作用。没有RA信号，太多的心肌细胞祖细胞在一个离散的区域内分化。影响心肌细胞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的是：1)确定类风湿关节炎信号水平如何影响斑马鱼心肌细胞祖细胞的分化；2)确定哪些RA受体调节心肌细胞祖细胞分化；3)寻找新的RA信号调节因子。

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.