两栖动物心室的发育
鸟类、哺乳动物和鳄鱼的心脏都有两个分开的心室,分别服务于单独的肺脏和系统循环。两栖类只有一个心室,但多数爬行类情况却不清楚。对一种蜥蜴(绿变色龙)和一种乌龟(滑龟)所做的一项新的胚胎学研究表明,先祖物种单一心室向两个心室的分化与“T-box转录因子”( Tbx5)的表达有关。
在鸟类和哺乳动物胚胎中,Tbx5表达限于左心室的前体。在乌龟和蜥蜴中,Tbx5最初在整个心室表达,但在乌龟(而非蜥蜴)中它后来限于在心室的左边表达。这说明,被改变的Tbx5表达,是推动胚胎心脏成形、为高能量陆地生活提供关键的适应性变化——完全被隔膜隔开的心脏——的一个可能的进化力量。与这一观点相一致的是,Tbx5功能丧失或扩大的小鼠会形成单一心室——既非左心室也非右心室。
原始出处:
Nature 461, 95-98 (3 September 2009) | doi:10.1038/nature08324
Reptilian heart development and the molecular basis of cardiac chamber evolution
Kazuko Koshiba-Takeuchi1,2,3,4,16, Alessandro D. Mori1,2,3,5,6,16, Bogac L. Kaynak1,2,3,16, Judith Cebra-Thomas7, Tatyana Sukonnik1,2,3, Romain O. Georges8, Stephany Latham9, Laural Beck9, R. Mark Henkelman10,11, Brian L. Black3,12, Eric N. Olson13, Juli Wade9, Jun K. Takeuchi4, Mona Nemer8,14, Scott F. Gilbert15 & Benoit G. Bruneau1,2,3,5,6
1 Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA
2 Department of Pediatrics,
3 Cardiovascular Research Institute, University of California, San Francisco, California 94158, USA
4 Division of Cardiovascular Research, Global-Edge Institute, Tokyo Institute of Technology, Yokohama, Kanagawa 226-8503, Japan
5 Program in Stem Cell and Developmental Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
6 Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada
7 Biology Department, Millersville University, Millersville, Pennsylvania 17551, USA
8 Institut de Recherches Cliniques de Montréal, Programme de Biologie Moléculaire, Université de Montréal, Montréal, Québec H3C 3J7, Canada
9 Department of Psychology and Program in Neuroscience, Michigan State University, East Lansing, Michigan 48824, USA
10 The Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
11 Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5S 1A8, Canada
12 Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA
13 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
14 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5 Canada
15 Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081, USA
16 These authors contributed equally to this work.
Correspondence to: Benoit G. Bruneau1,2,3,5,6 Correspondence and requests for materials should be addressed to B.G.B.
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 endothermy1, 2, 3. 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 ventricles4, 5, 6, 7? Here we examine 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 precursors8, 9. 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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