Macías D, Pérez-Pomares J M, García-Garrido L, Carmona R, Muñoz-Chápuli R
Departamento de Biología Animal, Facultad de Ciencias, Instituto Andaluz de Biotecnología, Universidad de Málaga, Spain.
Anat Embryol (Berl). 1998 Oct;198(4):307-15. doi: 10.1007/s004290050186.
Cardiac morphogenesis involves substantial remodeling processes that include cell transdifferentiation and migration. The c-ets-1 protooncogene codes for a transcription factor that can transactivate a number of genes involved in developmental processes such as degradation of extracellular matrices and cell migration. We have immunolocated the ets-1 protein in the heart of quail and chick embryos between the Hamburger and Hamilton stages HH16 and HH37. In HH16-17 embryos, the ets-1 transcription factor was only detected in some endocardial cells and in most mesothelial and mesenchymal cells of the proepicardium. Ets-1 immunoreactivity increased markedly in the developing endocardial cushions, myocardium, epicardium and early subepicardial mesenchyme of HH18-19 embryos. By HH20-24 the immunoreactivity was found throughout the heart, with a stronger intensity in the areas of epithelial-mesenchymal transition of the endocardium and epicardium. In embryos between HH26 and HH33, ets-1 immunoreactivity increased in the cushion mesenchyme, atrioventricular endocardium, ventricular epicardium and subepicardial mesenchyme cells, but not in other areas of the heart. The immunoreactivity declined in the innermost part of the endocardial cushions. The subepicardial mesenchyme was particularly immunoreactive in these stages, coinciding with the development of the subepicardial vascular network. In fact, ets-1 colocalized with the quail vascular marker QH1 in the subepicardial mesenchymal cells. Ets-1-negative cells were abundant in the subepicardium and valvuloseptal tissue of the HH37 embryos. The results suggest that ets-1, probably through transactivation of genes such as urokinase-type plasminogen activator and matrix metalloproteinases, might play a crucial role in the differentiation of the cushion and subepicardial mesenchyme, the formation of the intratrabecular sinusoids and the early development of the cardiac vessels.
心脏形态发生涉及大量重塑过程，包括细胞转分化和迁移。c-ets-1原癌基因编码一种转录因子，该转录因子可反式激活许多参与发育过程的基因，如细胞外基质降解和细胞迁移相关基因。我们已在汉堡和汉密尔顿分期HH16至HH37的鹌鹑和鸡胚胎心脏中对ets-1蛋白进行了免疫定位。在HH16 - 17胚胎中，仅在一些心内膜细胞以及前心外膜的大多数间皮和间充质细胞中检测到ets-1转录因子。在HH18 - 19胚胎发育中的心内膜垫、心肌、心外膜和早期心外膜下间充质中，ets-1免疫反应性显著增加。到HH20 - 24时，在整个心脏中都发现了免疫反应性，在心内膜和心外膜上皮-间充质转化区域强度更强。在HH26至HH33之间的胚胎中，ets-1免疫反应性在垫间充质、房室心内膜、心室心外膜和心外膜下间充质细胞中增加，但在心脏的其他区域未增加。心内膜垫最内部的免疫反应性下降。心外膜下间充质在这些阶段特别具有免疫反应性，这与心外膜下血管网络的发育一致。事实上，ets-1与鹌鹑血管标记物QH1在心外膜下间充质细胞中共定位。在HH37胚胎的心外膜和瓣膜间隔组织中，ets-1阴性细胞丰富。结果表明，ets-1可能通过反式激活诸如尿激酶型纤溶酶原激活剂和基质金属蛋白酶等基因，在垫和心外膜下间充质的分化、小梁内窦状隙的形成以及心脏血管的早期发育中发挥关键作用。
