The ascidian Mesp gene specifies heart precursor cells
The ascidian Mesp gene specifies heart precursor cells
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DOI：
10.1242/dev.01145
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发表时间：
2004-06-01
期刊：
影响因子：
4.6
通讯作者：
Satoh, N
中科院分区：
文献类型：
--
作者：
Satou, Y;Imai, KS;Satoh, N
了解心脏发育的分子基础是一个重要的研究领域，因为心血管系统畸形是最常见的先天性缺陷之一。尽管最近的研究已经确定了负责脊椎动物心脏形态发生的分子，但心脏祖细胞的初始特化尚未得到很好的表征。海鞘提供了一个适当的实验系统，探索这种规格的机制，因为谱系的少年心脏是很好的特点，B7.5细胞在110细胞阶段产生胚胎干腹侧细胞（TVC）或少年心脏祖细胞。在这里，我们表明，CS-Mesp，唯一的直系同源的脊椎动物Mesp基因在海鞘玻璃海鞘，特异性和瞬时表达的胚胎心脏祖细胞（B7.5细胞）。Cs-Mesp对于心脏前体细胞的特化是必不可少的，其中表达Nkx、HAND和HAND样（NoTrlc）基因。因此，用特异性吗啉代反义寡核苷酸敲低Cs-Mesp导致幼年心脏发育失败。与以前在小鼠中获得的证据一起，目前的结果表明，从Mesp到Nkx和HAND的心脏规格的机制在脊索动物中是保守的。
Understanding the molecular basis of heart development is an important research area, because malformation of the cardiovascular system is among the most frequent inborn defects. Although recent research has identified molecules responsible for heart morphogenesis in vertebrates, the initial specification of heart progenitors has not been well characterized. Ascidians provide an appropriate experimental system for exploring this specification mechanism, because the lineage for the juvenile heart is well characterized, with B7.5 cells at the 110-cell stage giving rise to embryonic trunk ventral cells (TVCs) or the juvenile heart progenitors. Here, we show that Cs-Mesp, the sole ortholog of vertebrate Mesp genes in the ascidian Ciona savignyi, is specifically and transiently expressed in the embryonic heart progenitor cells (B7.5 cells). Cs-Mesp is essential for the specification of heart precursor cells, in which Nkx, HAND and HAND-like (NoTrlc) genes are expressed. As a result, knockdown of Cs-Mesp with specific morpholino antisense oligonucleotides causes failure of the development of the juvenile heart. Together with previous evidence obtained in mice, the present results suggest that a mechanism for heart specification beginning with Mesp through Nkx and HAND is conserved among chordates.