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定向和分化。我们的小组最近发现了一个以前未知的次级心脏领域，在鸡胚中产生最终流出道的心肌。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道的失败导致主动脉错位。本申请的总体假设是，干细胞定型为心肌谱系的过程对于所有心肌祖细胞群体是共同的。在这些实验中要检验的具体假设是：（1）次级心脏场具有不同于初级心脏场的起源。这将使用三种最先进的鸡胚细胞示踪技术来确定。(2)次级心脏区域中的细胞向心肌谱系的定型是由在初级心脏区域中诱导心肌定型的相同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期间在流出道附近表达。该家族的特定成员，包括FGF-8和BMP-2，将以各种方式进行操作，以确定它们在诱导次级心脏野细胞分化为心肌中的作用。这些研究将建立次级心脏领域的发展历史。此外，由于流出心肌是心脏动脉极正确分隔的关键，这些研究将提高我们的知识，最终流出心肌的正常发展，并将提供新的见解圆锥动脉干畸形的基础。

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.