Reptilian heart development and the molecular basis of cardiac chamber evolution.

Reptilian heart development and the molecular basis of cardiac chamber evolution.
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DOI:
10.1038/nature08324
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发表时间:
2009-09-03
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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陆地生命的出现证明了对更复杂的循环系统的需要。在鸟类、哺乳动物和鳄鱼中,这已经演变成心脏完全分为左右两侧,允许分离的肺循环系统和体循环系统,这是恒温动物进化的关键要求。然而,人们对羊膜心脏的进化知之甚少。爬虫类动物的心脏在心脏分离的进化过程中一直是争论的主题:它们是只有一个心室还是有两个不完全分离的心室?我们研究了红耳滑龟(一种龟鳖)和绿耳滑龟(一种鳞鳖)的心脏发育,重点研究了发育中的心室中的基因表达。这两种爬行动物最初形成一个心室,均匀表达T-box转录因子基因Tbx5。相比之下,在鸟类和哺乳动物中,Tbx5仅限于左心室前体。在后期阶段,Tbx5在龟(而不是斑鸠)心脏中的表达逐渐局限于一个独特的左心室,形成一个左右梯度。这表明Tbx5的表达在进化过程中得到了完善,从而形成了脑室的模式。为了支持这一假设,我们发现Tbx5在小鼠心室中的缺失导致单个腔室缺乏明显的身份,表明Tbx5在分离中是必需的。重要的是,在整个发育中的心肌中,Tbx5的错误表达以模仿爬行动物的表达模式,也会导致单个室间隔缺失的错误表达。因此,心室分隔是由一个陡峭和正确定位的Tbx5梯度建立的。我们的发现为羊膜室的进化提供了分子机制,并支持了发育调节因子表达改变是脊椎动物进化的关键机制的概念。
The emergence of terrestrial life witnessed the need for more sophisticated circulatory systems. This has evolved in birds, mammals, and crocodilians into complete septation of the heart into left and right sides, allowing separate pulmonary and systemic circulatory systems, a key requirement for the evolution of endothermy. However, the evolution of the amniote heart is poorly understood. Reptilian hearts have been the subject of debate in the context of the evolution of cardiac septation: do they possess a single ventricular chamber or two incompletely septated ventricles? We examined heart development in the red-eared slider turtle, Trachemys scripta elegans (a chelonian), and the green anole, Anolis carolinensis (a squamate), focusing on gene expression in the developing ventricles. Both reptiles initially form a ventricular chamber that homogenously expresses the T-box transcription factor gene Tbx5. In contrast, in birds and mammals, Tbx5 is restricted to left ventricle precursors. In later stages, Tbx5 expression in the turtle (but not anole) heart is gradually restricted to a distinct left ventricle, forming a left-right gradient. This suggests that Tbx5 expression was refined during evolution to pattern the ventricles. In support of this hypothesis, we show that loss of Tbx5 in the mouse ventricle results in a single chamber lacking distinct identity, indicating a requirement for Tbx5 in septation. Importantly, misexpression of Tbx5 throughout the developing myocardium to mimic the reptilian expression pattern also results in a single mispatterned ventricular chamber lacking septation. Thus, ventricular septation is established by a steep and correctly positioned Tbx5 gradient. Our findings provide a molecular mechanism for the evolution of the amniote ventricle, and support the concept that altered expression of developmental regulators is a key mechanism of vertebrate evolution.
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