Lopez-Sanchez Carmen, Climent Vicente, Schoenwolf Gary C, Alvarez Ignacio S, Garcia-Martinez Virginio
Departamento de Ciencias Morfológicas y Biología Celular y Animal, Facultad de Medicina, Universidad de Extremadura, Apartado 108, 06080 Badajoz, Spain.
Cell Tissue Res. 2002 Aug;309(2):237-49. doi: 10.1007/s00441-002-0567-2. Epub 2002 Jun 26.
The earliest events underlying cardiac induction and morphogenesis remain largely unknown. In the present study, we show that Hensen's node, the organizer of the avian embryo, induces cardiogenesis. Specifically, following heterotopic transplantation, Hensen's node induces ectopic host tissue that expresses two early cardiac markers ( cNkx-2.5 and cNkx-2.8), as well as a ventricular marker ( VMHC1), but not an atrial marker ( AMHC1). Moreover, we examine the potential roles of candidate growth factors known to be secreted by Hensen's node. Our results show that fibroblast growth factors (FGF-2 and FGF-4) when ectopically expressed can initiate cardiac development, inducing host tissue to express the two cardiac transcription factors cNkx-2.5 and cNkx-2.8, as well as the cardiac-restricted structural gene VMHC1, but not AMHC1. In contrast to FGFs, TGFbeta family members fail to induce ectopic tissue and expression of cardiac marker genes. We also examined the effects of growth factors on the morphogenesis of the host embryo's heart. Both exogenous FGFs and TGFbeta family members perturb normal morphogenesis of the early cardiac tube and alter patterns of ventricular and atria gene expression in characteristic ways. Namely, exogenous FGFs expand areas expressing the ventricular marker VMHC1 at the expense of areas expressing the atrial marker AMHC1. Conversely, exogenous TGFbeta1 inhibits expression of VMHC1, expanding AMHC1 expression. We show here that Hensen's node and FGFs induce ectopic expression of cardiac lineage markers, and that FGF and TGFbeta family members can modulate early development of the heart. Collectively, these data suggest that the organizer plays a crucial role in cardiac induction and morphogenesis, mediated in part by endogenous members of the FGF and TGFbeta families.
心脏诱导和形态发生的最早事件在很大程度上仍然未知。在本研究中,我们表明亨氏结,即鸟类胚胎的组织者,可诱导心脏发生。具体而言,异位移植后,亨氏结可诱导异位宿主组织表达两种早期心脏标志物(cNkx - 2.5和cNkx - 2.8)以及一种心室标志物(VMHC1),但不表达心房标志物(AMHC1)。此外,我们研究了已知由亨氏结分泌的候选生长因子的潜在作用。我们的结果表明,成纤维细胞生长因子(FGF - 2和FGF - 4)异位表达时可启动心脏发育,诱导宿主组织表达两种心脏转录因子cNkx - 2.5和cNkx - 2.8以及心脏特异性结构基因VMHC1,但不表达AMHC1。与成纤维细胞生长因子相反,转化生长因子β家族成员未能诱导异位组织和心脏标志物基因的表达。我们还研究了生长因子对宿主胚胎心脏形态发生的影响。外源性成纤维细胞生长因子和转化生长因子β家族成员均会扰乱早期心管的正常形态发生,并以特征性方式改变心室和心房基因表达模式。具体而言,外源性成纤维细胞生长因子会以牺牲表达心房标志物AMHC1的区域为代价,扩大表达心室标志物VMHC1的区域。相反,外源性转化生长因子β1会抑制VMHC1的表达,扩大AMHC1的表达。我们在此表明,亨氏结和成纤维细胞生长因子可诱导心脏谱系标志物的异位表达,并且成纤维细胞生长因子和转化生长因子β家族成员可调节心脏的早期发育。总体而言,这些数据表明组织者在心脏诱导和形态发生中起关键作用,部分由成纤维细胞生长因子和转化生长因子β家族的内源性成员介导。