At the heart of the matter

Abstract

True to the assertion of Leonardo da Vinci in 1513, that it would need a whole book to describe the heart in words, it in fact takes two volumes of ‘Heart Development and Regeneration’ just to give a snapshot of this topic in 2010. This book is the sequel to the multi-authored volume ‘Heart Development’, which was published in 1998 and co-edited by Harvey and Rosenthal. However, ‘Heart Development and Regeneration’ is a completely new rendition: the contents encompass cutting-edge contemporary topics, including epigenetic control of heart development, the biology of progenitor and stem cells, and regeneration of heart tissues, as well as an in-depth coverage of conventional subjects such as cardiac tissue precursors and heart fields, patterning of the heart tube, development of epicardium, septation and chamber formation, establishment of asymmetry, transcriptional control of cardiogenesis and vasculogenesis, and heart development in model organisms. In total, there are 46 chapters grouped into 14 parts, with the discourse on conventional subjects included in Volume 1 and the emerging topics in Volume 2. A surprise bonus is that readers are enchanted by the stunningly beautiful artwork of the Heart Plates by Nadia Rosenthal while thumbing through its pages.Given the broad scope of ‘Heart Development and Regeneration’, readers of Disease Models & Mechanisms with interests in any aspect of heart diseases will almost certainly find this book useful. Overall, the content focuses on mammalian species, and mainly on mice, which are particularly advantageous given the wealth of knowledge gained through recent ‘omics’ approaches and the availability of mouse genetic and mutant resources. In general, limitations of studying cardiogenesis in the mouse are complemented by experimental studies of technically more amenable organisms, such as the zebrafish (Chapters 1.4 and 12.2) and the chick (Chapters 1.5 and 7.1), and by molecular analysis of gene function and signaling pathways in Drosophila (Chapter 1.2) and Xenopus (Chapter 1.3). However, irrespective of the model organism one chooses to work with, a good understanding of the evodevo characteristics of the heart and vascular structures is essential for translating knowledge about a particular model organism to the human heart and the diseases that affect it. In this regard, the chapters on the evolutionary origin of hearts (Chapter 1.1) and endothelial cells (Chapter 8.1) are the ‘must-read’ sections. From here, one can delve further into details of disease mechanisms, such as morphological aspects of heart malformations or the molecular mechanisms that underpin heart development and disease.The heart is a cleverly engineered organ that truly illustrates the connection between anatomical form and physiological function. Many of this organ’s functional attributes can be understood through studying its evolution and the developmental strategy that allows it to take shape in the embryo. For readers who are embryologically inclined, this book provides a great deal of information on the early morphogenesis of the heart, collated meticulously from data of developmental biological and genetic studies; topics range from fate maps, lineage relationships, tissue induction, the acquisition of left-right asymmetry, and the formation of heart tube, chambers, heart valves and outflow tracts (Parts 2–7). These basic paradigms of heart development are a valuable foundation for understanding the pathogenic mechanisms of developmental diseases of the heart.A crucial prerequisite for elucidating the developmental basis of heart malformations is that anatomical defects are described systematically using standardized vocabulary and descriptors. To this end, a system of sequential segmental analysis for documenting structural defects is proposed (Chapter 3.4). To further expand on the mechanisms of heart malformations, the book discusses how chemical mutagenesis can be used in phenotypic screens for heart defects in mice (Chapter 11.2). Of particular interest is the application of electrocardiography, as well as ultrasound, episcopic and magnetic resonance imaging technologies (discussed in Chapter 11.3), which can enhance the throughput of such screens for developing heart disease models.Remarkably, despite the anatomical variation of the heart among different animal species, its formation is driven by a highly conserved set of molecular players acting in a multitude of genetic networks (Part 9). It is evident that a significant editorial effort has been made to achieve a uniform and lucid style of presentation when describing the role of the molecular determinants in cardiac development, and their association with malformations (Chapters 9.1–9.5). In Part 10, the reader is indulged with insights into the epigenetic control of heart development and diseases, with chapters on chromatin modification, histone deacetylation factors and microRNAs; particularly intriguing is the balancing act of miR-1 and miR-133 in guiding myogenic differentiation. One might expect the section on cardiomics (Part 11) to be a primer of the system-based analysis of ‘omics’ data, containing insights into the interaction between transcriptional networks and signaling pathways in cardiac development and function. However, in reality the chapters on genomics and proteomics (Chapters 11.1, 11.4 and 11.5) focus mainly on technologies. Although this approach has its merits, there would be room in a future sequel to expand on the biological relevance of transcriptional and proteomic information, and also to formulate a systems-biological overview of the cross-action of the many genetic and molecular circuits in heart function, development and disease.A reflection of the contemporary trend in heart research is the inclusion of eight chapters on cardiac progenitor and stem cells, and their applications in cell-based therapy, and heart tissue repair and regeneration. Recent progress in these areas is evident in that none of the 28 chapters of the previous book, ‘Heart Development’, was dedicated to these topics. The fields of cardiac stem and/or progenitor cells and tissue regeneration are still in their infancy, so this is therefore an ideal time to take stock of the current state of play and to explore the future trajectory of research. Cardiac regeneration in mammals is hampered by adverse tissue reaction to injury, which impacts on the reparative activity. Some useful lessons on how to enhance regeneration or repair might be learned by studying the zebrafish heart, which is capable of efficient tissue regeneration and functional recovery (Chapter 12.2). Various potential avenues to accomplish this goal are highlighted in the discussion of the characterization and mobilization of different types of stem cells (Chapters 13.2, 14.1 and 14.2). Recent research and clinical studies have revealed that revascularization of injured tissues is instrumental for cardiac muscle recovery (Chapter 14.2). Future pursuit to rebuild the vascular network for cardiac tissue recovery will require a detailed knowledge of mechanisms of vasculogenesis (Chapter 8.2).This is a monumental book for which the editors and contributors are truly deserving of praise for its high-quality content. It is the ideal introductory reading for post-docs and students who are venturing into heart research, and the first port of call for seasoned investigators needing an update on an unfamiliar topic. In view of the rapid progress in this field, readers will gain most from the up-to-date content now, at its time of publication. However, the book’s elegantly articulated description of the fundamental concepts of heart biology means it will be a benchmark reference for years to come.Cover image reproduced with permission from Elsevier.