Xapelin and Xmsr are required for cardiovascular development in Xenopus laevis

Xapelin and Xmsr are required for cardiovascular development in Xenopus laevis
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DOI:
10.1016/j.ydbio.2006.06.028
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发表时间:
2006-10-01
影响因子:
2.7
通讯作者:
Asashima, Makoto
Asashima, Makoto
中科院分区:
生物学3区
文献类型:
--
作者:
Inui, Masafumi;Fukui, Akimasa;Asashima, Makoto

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心血管发育是一个复杂的过程,尽管有大量的研究,但内皮、造血和心脏发育的机制以及这些过程之间的相互关系尚未完全了解。在这项研究中,我们证明了非洲爪蟾apelin和Xmsr在心血管发育中起着关键作用。Apelin是最近鉴定的孤儿G蛋白偶联受体APJ的配体,并且参与哺乳动物的流体稳态。非洲爪蟾前原爱帕琳(Xpreproapelin)被分离并且其mRNA定位于假定血管周围的区域,其与表达Xmsr的血管重叠或相邻,Xpreproapelin的过表达扰乱了内皮前体细胞标志物XIFli和造血前体细胞标志物SCL在神经胚处的表达,而注射Xapelin和Xmsr的吗啉代反义寡核苷酸的胚胎显示Tie 2、α-珠蛋白、XPOX 2和cTnI(分别是内皮细胞、红细胞、髓样细胞和心肌细胞的标志物)的表达减弱。XIFli吗啉代对心脏分化具有与Xapelin和Xmsr吗啉代类似的作用,表明内皮和心脏分化之间的意想不到的潜在关系。组成型活性G α i的强制表达挽救了注射Xmsr吗啉代的胚胎的表型,表明I/O型G蛋白α亚基在Xmsr下游起作用。(c)2006年爱思唯尔公司All rights reserved.
The cardiovascular development is the elaborate process, and despite the extensive studies, the mechanisms underlying endothelial, hematopoietic, and cardiac developments, as well as the interrelation between these processes, are not fully understood. In this study, we demonstrated that Xenopus apelin and Xmsr play pivotal roles in cardiovascular development. Apelin is a recently identified ligand for an orphan G-protein-coupled receptor APJ and is involved in fluid homeostasis in mammals. Xenopus preproapelin (Xpreproapelin) was isolated and its mRNA localized to the region around the presumptive blood vessels, which are overlapping or adjacent to those expressing Xmsr, the Xenopus homologue of APJ Overexpression of Xpreproapelin disorganized the expression of the endothelial precursor cell marker XlFli and the hematopoietic precursor cell marker SCL at the neurula, whereas embryos injected with morpholino antisense oligonucleotides for Xapelin and Xmsr displayed attenuated expression of Tie2, alpha-globin, XPOX2, and cTnI, markers of endothelium, erythrocytes, myeloid cells, and cardiomyocytes, respectively. XlFli morpholino had similar effects to Xapelin and Xmsr morpholinos on cardiac differentiation, suggesting an unexpected potential relationship between the endothelium and cardiac differentiation. Forced expression of constitutive active G alpha i rescued the phenotypes of Xmsr morpholino-injected embryos, indicating that the i/o type of G protein alpha subunit acts downstream of Xmsr. (c) 2006 Elsevier Inc. All rights reserved.