Characterization of Secondary Heart Field

描述（由申请人提供）：本提案的长期目标是了解干细胞向心肌谱系的承诺和分化。我们的研究小组最近在鸡胚胎中发现了一种以前未知的产生最终流出道心肌的次级心脏场。我们发现，在心脏循环过程中，通过添加来自次级心野的心肌细胞来延长流出物的失败会导致主动脉右倾。该应用的总体假设是，干细胞对心肌谱系的承诺过程对所有心肌祖细胞群体都是共同的。在这些实验中要检验的具体假设是：(1)次级心野的起源不同于初级心野。这将通过三种最先进的小鸡胚胎细胞追踪技术来确定。(2)次级心脏野细胞向心肌谱系的承托是由诱导初级心脏野心肌承托的生长因子家族的成员诱导的。tgf - β和FGF家族成员在流出道延长过程中在流出道附近表达。该家族的特定成员，包括FGF-8和BMP-2，将通过多种方式进行操纵，以确定它们在诱导继发性心野细胞向心肌分化中的作用。所提出的研究将建立继发性心脏领域的发展历史。此外，由于流出心肌对于心脏动脉极的正确分离至关重要，这些研究将增强我们对最终流出心肌正常发育的认识，并将为圆锥锥体畸形的基础提供新的见解。

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to understand stem cell commitment and differentiation to a myocardial lineage. Our group has recently discovered a previously unknown secondary heart field that produces the myocardium of the definitive outflow tract in chick embryos. We have found that failure of outflow lengthening by addition of myocardial cells from the secondary heart field during cardiac looping results in dextroposed aorta. The overall hypothesis of the application is that the process of stem cell commitment to a myocardial lineage is common to all myocardial progenitor populations. The specific hypotheses to be tested in these experiments are: (1) The secondary heart field has an origin distinct from the primary heart field. This will be determined using three state-of-the-art cell tracing techniques in chick embryos. (2) Commitment of cells in the secondary heart field to the myocardial lineage is induced by members of the same growth factor families that induce myocardial commitment in the primary heart fields. TGFbeta and FGF family members are expressed in proximity to the outflow tract during its lengthening. Specific members of this family, including FGF-8 and BMP-2, will be manipulated in a variety of ways to determine their role in inducing differentiation of secondary heart field cells into myocardium. The studies proposed will establish the developmental history of the secondary heart field. Furthermore, because the outflow myocardium is critical for correct septation of the arterial pole of the heart, these studies will enhance our knowledge of normal development of the definitive outflow myocardium, and will provide new insights into the basis of conotruncal malformations.