Cardiac Development and Animal Models of Congenital Heart Defects
The major events of cardiac development, including early heart formation, chamber morphogenesis and septation, as well as conduction system and coronary artery development, are briefly reviewed together with a short introduction to the animal species comm
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Cardiac Development and Animal Models of Congenital Heart Defects Robert G. Kelly
Contents 1.1 Introduction 1.2 From the Cardiac Crescent to the Embryonic Heart Tube 1.3 Ballooning Morphogenesis and Cardiac Septation 1.4 Development of the Conduction System and Coronary Circulation 1.5 Animal Models of Heart Development References
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Abstract
The major events of cardiac development, including early heart formation, chamber morphogenesis and septation, as well as conduction system and coronary artery development, are briefly reviewed together with a short introduction to the animal species commonly used to study heart development and model congenital heart defects.
1.1
Introduction
This chapter provides a brief overview of the major events of cardiac development as well as the animal models used to study the developing heart. We will focus on the sequence of events that occur during mouse heart development, the principal animal model used for genetic studies of heart development. Mouse heart development and the structure of the definitive mouse heart are highly conserved with humans, with evident R.G. Kelly Aix Marseille Université, Institut de Biologie du Dévelopment de Marseille, Marseille, France e-mail: [email protected] © Springer-Verlag Wien 2016 S. Rickert-Sperling et al. (eds.), Congenital Heart Diseases: The Broken Heart: Clinical Features, Human Genetics and Molecular Pathways, DOI 10.1007/978-3-7091-1883-2_1
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differences in scale, both temporal and spatial [1]. The advantages of the mouse are discussed in the animal models section below (1.5) and have led to the generation of numerous mouse congenital heart disease (CHD) models [2]. The goal here is to provide an introduction to the chapters in Part I as well as to the pathways and models sections; the majority of the references in this introductory chapter are reviews, to which the reader seeking further information is directed. For a detailed description of human heart development, the reader is referred to embryology textbooks such as Larsen’s Human Embryology or Langman’s Medical Embryology [3, 4].
1.2
From the Cardiac Crescent to the Embryonic Heart Tube
The central week of mouse gestation, corresponding approximately to weeks 2–5 of human embryonic development, spans the onset of cardiac differentiation through to the completion of cardiac septation (Fig. 1.1). Cardiomyocytes first differentiate in the most anterior lateral region of splanchnic mesoderm underlying the neural folds [5]. Bilateral cardiac progenitor populations converge at the ventral midline to generate the cardiac crescent by embryonic day (E) 7.5 (Fig. 1.1a). These myocardial cells are specified by a combination of positive intercellular signals from surrounding embryonic tissues, including foregut endoderm and surface ectoderm, and negative signals from midline structures. These inputs result in the precise activation of cardiac transcription factors that combinatorially drive the cardiomyogenic program in the cardiac crescent [6]. Thes
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