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在非洲爪蟾心脏发育过程中表达的与锡心人相关的基因。

tinman-related genes expressed during heart development in Xenopus.

作者信息

Newman C S, Krieg P A

机构信息

Institute for Cellular and Molecular Biology, University of Texas at Austin 78712, USA.

出版信息

Dev Genet. 1998;22(3):230-8. doi: 10.1002/(SICI)1520-6408(1998)22:3<230::AID-DVG5>3.0.CO;2-7.

Abstract

The tinman homeobox gene of Drosophila is absolutely required for development of the insect heart. This observation prompted the isolation of tinman-related genes from vertebrates, in the hope that the developmental function of the gene would be conserved between evolutionarily distinct species. The first vertebrate tinman gene, Nkx2-5, was isolated from mouse and subsequently, orthologues of Nkx2-5 have been isolated from a number of different species. In all cases, a conserved pattern of Nkx2-5 expression is observed in the developing heart, commencing prior to differentiation. Genetic ablation of Nkx2-5 in the mouse results in embryonic lethality due to heart defects, but most myocardial genes are expressed normally and a beating heart tube forms. This observation raises the possibility that additional genes related to Nkx2-5 are partially rescuing Nkx2-5 function in the null mouse. Recently, additional members of the tinman-related gene family have been discovered and characterized in a number of different species. Somewhat surprisingly, orthologous genes in different organisms can be rather divergent in sequence and may show completely different expression patterns. In at least some organisms, expression of the tinman-related genes is not observed in the heart. Due to the increasing number of family members and the somewhat divergent expression patterns, the precise role of the tinman-related genes in cardiac development remains an open question. In a search for additional tinman-related genes in the frog, Xenopus laevis, we have identified Nkx2-9, a novel member of the tinman-related gene family. Preliminary characterization reveals that Nkx2-9 is expressed in the cardiogenic region of the embryo prior to differentiation, but transcript levels decrease rapidly, in the heart, at about the time that differentiation commences.

摘要

果蝇的锡人同源框基因对于昆虫心脏的发育是绝对必需的。这一观察结果促使人们从脊椎动物中分离出与锡人相关的基因,希望该基因的发育功能在进化上不同的物种之间能够保守。第一个脊椎动物锡人基因Nkx2 - 5是从小鼠中分离出来的,随后,Nkx2 - 5的直系同源基因已从许多不同物种中分离出来。在所有情况下,在发育中的心脏中都观察到Nkx2 - 5的保守表达模式,这种表达在分化之前就开始了。在小鼠中对Nkx2 - 5进行基因敲除会因心脏缺陷导致胚胎致死,但大多数心肌基因仍正常表达,并且会形成跳动的心脏管。这一观察结果增加了一种可能性,即与Nkx2 - 5相关的其他基因在基因敲除小鼠中部分挽救了Nkx2 - 5的功能。最近,在许多不同物种中发现并鉴定了与锡人相关基因家族的其他成员。有点令人惊讶的是,不同生物体中的直系同源基因在序列上可能有很大差异,并且可能表现出完全不同的表达模式。在至少一些生物体中,未在心脏中观察到与锡人相关基因的表达。由于家族成员数量的增加以及表达模式的某种差异,与锡人相关的基因在心脏发育中的精确作用仍然是一个悬而未决的问题。在对非洲爪蟾(Xenopus laevis)中其他与锡人相关基因的搜索中,我们鉴定出了Nkx2 - 9,它是与锡人相关基因家族的一个新成员。初步特征表明,Nkx2 - 9在胚胎分化前在心源性区域表达,但在分化开始时,心脏中的转录水平迅速下降。

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