Abstract

Cardiac development is a complex developmental process that is initiated soon after gastrulation, as two sets of precardiac mesodermal precursors are symmetrically located and subsequently fused at the embryonic midline forming the cardiac straight tube. Thereafter, the cardiac straight tube invariably bends to the right, configuring the first sign of morphological left–right asymmetry and soon thereafter the atrial and ventricular chambers are formed, expanded and progressively septated. As a consequence of all these morphogenetic processes, the fetal heart acquired a four-chambered structure having distinct inlet and outlet connections and a specialized conduction system capable of directing the electrical impulse within the fully formed heart. Over the last decades, our understanding of the morphogenetic, cellular, and molecular pathways involved in cardiac development has exponentially grown. Multiples aspects of the initial discoveries during heart formation has served as guiding tools to understand the etiology of cardiac congenital anomalies and adult cardiac pathology, as well as to enlighten novels approaches to heal the damaged heart. In this review we provide an overview of the complex cellular and molecular pathways driving heart morphogenesis and how those discoveries have provided new roads into the genetic, clinical and therapeutic management of the diseased hearts.

Highlights

  • Over the last decades, our understanding of the cellular and molecular mechanisms driving cardiac development has greatly increased

  • The generating patient specific induced pluripotent stem cells [399] and opens up new tools for personalized drug testing and reparative medicine. Instructive signals such as those provided by Tbx2 and Tbx3 configure the precursor backbone of the cardiac conduction system, while the atrial and ventricular chambers are mainly specified by the expression of Hey, Hrt and Irx transcription factors [191,192,193,194,195,196]

  • We have provided in this review an overview of the cellular and molecular mechanisms that contribute to cardiac development, we aware that it only provides a glimpse of those previously reported mechanisms

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Summary

Introduction

Our understanding of the cellular and molecular mechanisms driving cardiac development has greatly increased. Such discoveries have provided clues to dissect the genetic and molecular bases of congenital heart diseases, as well as provided tools to configure novel cellular and molecular approaches to heal the damaged heart. We provide a comprehensive summary of the cellular and molecular pathways involved in heart formation, and translational contribution of such findings. This review will allow clinical cardiologists to discover the contributions of basic cardiovascular development to the clinics and to cardiovascular developmental biologists to envision their therapeutic and clinical potentials

From Gastrulation to the Early Cardiac Linear Tube
Clinical and Translational Perspectives of Early Cardiogenic Development
Cardiac Linear Heart and Left–Right Symmetry Break
Clinical and Translational Perspectives of Left–Right Symmetry Break
Cardiac Ballooning and the Configuration Cardiac Conductive System
Atrial Septation
Atrioventricular Septation
Ventricular Septation
Outflow Tract Septation and Aortic Arch Remodeling
1.10. Clinical and Translational Perspectives of Cardiac Septation
Conclusions
Perspectives
Methods
A Mouse Model of Congenital Heart Disease
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