Lack of regulation in the heart forming region of avian embryos

Lack of regulation in the heart forming region of avian embryos
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DOI:
10.1006/dbio.1998.9167
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发表时间:
1999-03-01
影响因子:
2.7
通讯作者:
Yutzey, KE
Yutzey, KE
中科院分区:
生物学3区
文献类型:
--
作者:
Ehrman, LA;Yutzey, KE

文献摘要

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心源性中胚层消融后再生心脏的能力已在早期鱼类和两栖动物胚胎中得到证实,但这种类型的心脏场调节尚未在鸟类或哺乳动物中发现。在禽类胚胎中研究了心源性中胚层的调节潜力,并与早期心脏发生中涉及的基因的空间表达有关。随着早期心脏调节因子如bmp-2和nkx-2.5的鉴定,现在有可能使经典的胚胎学研究与体内心脏谱系决定的分子机制相一致。最前外侧的胚胎细胞被鉴定为成为心脏的区域,并且去除这些细胞的全部或任何子集导致相应心脏结构的丧失。此外,去除形成心脏的侧部中胚层而保持侧部内胚层完整也导致心脏结构的损失。因此,即使存在潜在的心脏诱导内胚层,内侧前中胚层也不能在体内被募集到心脏谱系中。原位分析表明,与心脏发生早期事件有关的基因,如骨形态发生蛋白2(bmp-2)和nkx-2.5,与远外侧心脏形成区的映射一致。激活素IIa型受体(actR-IIa)是BMP信号传导的潜在介体,因为它在整个前中胚层中表达,其中最高水平的表达发生在侧向预期心脏细胞中。actR-IIa的后边界与nkx-2.5表达的后边界一致,支持ActR-IIa参与将心脏形成区域限制于暴露于BMP-2的外侧细胞的前亚群的模型。对nkx-2.5和actR-IIa表达后的侧板中胚层的心源性潜力的分析表明,这些细胞在体外不是心源性的,并且从胚胎中去除这些细胞不会导致体内心脏组织的损失。因此,将成为心脏的禽类胚胎区域由nkx-2.5基因表达的内侧、外侧和后侧定义。去除全部或部分nkx-2.5表达区域导致相应心脏结构的丧失,表明在nkx-2.5表达开始后的阶段,鸡胚不能在体内再生心脏组织,(C)1999 Academic Press。
The ability to regenerate a heart after ablation of cardiogenic mesoderm has been demonstrated in early stage fish and amphibian embryos but this type of regulation of the heart field has not been seen in avians or mammals. The regulative potential of the cardiogenic mesoderm was examined in avian embryos and related to the spatial expression of genes implicated in early cardiogenesis. With the identification of early cardiac regulators such as bmp-2 and nkx-2.5, it is now possible to reconcile classical embryological studies with molecular mechanisms of cardiac lineage determination in vivo. The most anterior lateral embryonic cells were identified as the region that becomes the heart and removal of all or any subset of these cells resulted in the loss of corresponding cardiac structures. In addition, removal of the lateral heart forming mesoderm while leaving the lateral endoderm intact also results in loss of cardiac structures. Thus the medial anterior mesoderm cannot be recruited into the heart lineage in vivo even in the presence of potentially cardiac inducing endoderm. In situ analysis demonstrated that genes involved in early events of cardiogenesis such as bone morphogenetic protein 2 (bmp-2) and nkx-2.5 are expressed coincidentally with the mapped far lateral heart forming region. The activin type IIa receptor (actR-IIa) is a potential mediator of BMP signaling since it is expressed throughout the anterior mesoderm with the highest level of expression occurring in the lateral prospective heart cells. The posterior boundary of actR-IIa is consistent with the posterior boundary of nkx-2.5 expression, supporting a model whereby ActR-IIa is involved in restricting the heart forming region to an anterior subset of lateral cells exposed to BMP-2. Analysis of the cardiogenic potential of the lateral plate mesoderm posterior to nkx-2.5 and actR-IIa expression demonstrated that these cells are not cardiogenic in vitro and that removal of these cells from the embryo does not result in loss of heart tissue in vivo. Thus, the region of the avian embryo that will become the heart is defined medially, laterally, and posteriorly by nkx-2.5 gene expression. Removal of all or part of the nkx-2.5 expressing region results in the loss of corresponding heart structures, demonstrating the inability of the chick embryo to regenerate cardiac tissue in vivo at stages after nkx-2.5 expression is initiated, (C) 1999 Academic Press.