Reptilian heart development and the molecular basis of cardiac chamber evolution

Abstract

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 endothermy1–3. 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 ventricles4–7? 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 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.

Tbx5 et l’adaptation du cœur à la vie sur terre

“…Tbx5 étant conservé durant l'évolution, il importait, dans un premier temps, d'établir son patron d'expression chez les différentes espèces. À cette fin, K. Koshiba-Takeuchi et al se sont servis de deux reptiles ayant un coeur en transition entre 3 et 4 chambres : la tortue d'eau douce à oreilles rouges Trachemys scripta elegans et le lézard vert Anolis carolinensis ; le premier possède un coeur plus proche de celui à 4 chambres, celui du second s'apparente à un coeur à 3 chambres [2]. Durant les premiers stades de la formation du coeur chez les deux reptiles, Tbx5 est observé dans toute la cavité ventriculaire embryonnaire.…”

“…Les divergences structurales et fonctionnelles des organes entre les espèces [1] seraient attribuables à ces changements plutôt qu'à l'existence de gènes additionnels. L'article de K. Koshiba-Takeuchi et al, publié dans Nature fin 2009, confirme cette hypothèse en mettant en évi-dence le rôle joué par le facteur de transcription Tbx5 dans la formation du septum ventriculaire, étape importante de l'évolution darwinienne des vertébrés car elle est nécessaire à leur adaptation au mode de vie sur terre [2]. De plus, les malformations des septa qui séparent les 4 chambres cardiaques comptent parmi les défauts de naissance les plus fréquents chez l'humain.…”

Combinatorial Functions of Transcription Factors and Epigenetic Factors in Heart Development and Disease

“…Tbx5 and Sall4 participate in protein-protein interactions and synergistically regulate downstream gene expression [13]. Furthermore, Tbx5 is a key gene involved in the acquisition of the ventricular septum during vertebrate evolution [14]. During vertebrate evolution from aquatic to terrestrial life, the morphology of the heart has changed.…”

Live optical projection tomography

“…The range of species successfully imaged now includes human, 9 mouse, 10,11 chick, 12 reptile species, 13 zebrafish, 14 Drosophila 15 and Arabidopsis. 16 Mouse embryos are routinely imaged at E9.5 up to E12.5, 17 and, for older specimens, organs in isolation are scanned, for example, the developing limb 18 or brain 19 at E14.5.…”