Tirosh-Finkel Libbat, Elhanany Hadas, Rinon Ariel, Tzahor Eldad
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
Development. 2006 May;133(10):1943-53. doi: 10.1242/dev.02365. Epub 2006 Apr 19.
During early embryogenesis, heart and skeletal muscle progenitor cells are thought to derive from distinct regions of the mesoderm (i.e. the lateral plate mesoderm and paraxial mesoderm, respectively). In the present study, we have employed both in vitro and in vivo experimental systems in the avian embryo to explore how mesoderm progenitors in the head differentiate into both heart and skeletal muscles. Using fate-mapping studies, gene expression analyses, and manipulation of signaling pathways in the chick embryo, we demonstrate that cells from the cranial paraxial mesoderm contribute to both myocardial and endocardial cell populations within the cardiac outflow tract. We further show that Bmp signaling affects the specification of mesoderm cells in the head: application of Bmp4, both in vitro and in vivo, induces cardiac differentiation in the cranial paraxial mesoderm and blocks the differentiation of skeletal muscle precursors in these cells. Our results demonstrate that cells within the cranial paraxial mesoderm play a vital role in cardiogenesis, as a new source of cardiac progenitors that populate the cardiac outflow tract in vivo. A deeper understanding of mesodermal lineage specification in the vertebrate head is expected to provide insights into the normal, as well as pathological, aspects of heart and craniofacial development.
在胚胎发育早期，心脏和骨骼肌祖细胞被认为分别来源于中胚层的不同区域（即侧板中胚层和轴旁中胚层）。在本研究中，我们利用鸟类胚胎中的体外和体内实验系统，探究头部的中胚层祖细胞如何分化为心脏和骨骼肌。通过命运图谱研究、基因表达分析以及对鸡胚信号通路的操控，我们证明颅轴旁中胚层的细胞对心脏流出道内的心肌和心内膜细胞群体均有贡献。我们进一步表明，Bmp信号影响头部中胚层细胞的特化：在体外和体内应用Bmp4均可诱导颅轴旁中胚层的心脏分化，并阻止这些细胞中骨骼肌前体的分化。我们的结果表明，颅轴旁中胚层内的细胞在心脏发生过程中起着至关重要的作用，作为一种新的心脏祖细胞来源，在体内填充心脏流出道。对脊椎动物头部中胚层谱系特化的更深入理解有望为心脏和颅面发育的正常以及病理方面提供见解。
