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Epicardial Development and Cardiovascular Disease
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Epicardial Development and Cardiovascular Disease

A special issue of Journal of Developmental Biology (ISSN 2221-3759).

Deadline for manuscript submissions: closed (1 May 2013) | Viewed by 147018

Special Issue Editors

Prof. Dr. Thomas Brand

E-Mail Website
Guest Editor
National Heart & Lung Institute, Imperial College London, Hammersmith Campus, London W12 0NN, UK
Interests: heart development; cardiac pacemaker development and function; popeye genes; cAMP signaling
Special Issues, Collections and Topics in MDPI journals
Dr. Maurice Van den Hoff

E-Mail Website1 Website2
Guest Editor
Department of Medical Biology, Academic Medical Center, Meibergdreef 15, 1105AZ Amsterdam, The Netherlands
Interests: cardiovascular development; epicardium development; myocardium formation; cell signalling; BMP signalling; molecular biology; transgenic mice; congenital cardiac abnormalities
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The proepicardium is an embryonic structure, which develops at the venous pole and gives rise to the epicardium and cells of the cardiac interstitium (fibroblast and smooth muscle cells). Its contribution to the endothelium is under intense debate and there may be even species-specific differences. The epicardium has an important role later in development as a source of growth signals, which will stimulate the expansion of the ventricular wall in order to provide sufficient cardiac output and to match the demands of the growing embryo. The epicardium has recently also received significant attention because of its involvement in cardiac regeneration, which has been mainly studied in the zebrafish and murine model systems. In the mammalian heart there is strong evidence that the epicardium of the adult heart is a source for cardiac stem cells, possibly involved in wound healing and scar formation in response to injury. Several different model systems have been employed in the past years including cyclostomes, zebrafish, Xenopus, chicken and mice and this special issue of the Journal of Developmental Biology will provide a comprehensive overview of the current standing of this research field. Leading experts have agreed to contribute review articles on this exciting topic. Research papers on epicardial development and the role of the epicardium in cardiac regeneration are welcome contributions to this special issue.

Prof. Thomas Brand
Dr. Maurice van den Hoff
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Developmental Biology is an international peer-reviewed open access quarterly journal published by MDPI.

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Published Papers (16 papers)

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1573 KiB  
Article
The Epicardium in the Embryonic and Adult Zebrafish
by Marina Peralta, Juan Manuel González-Rosa, Inês Joao Marques and Nadia Mercader
J. Dev. Biol. 2014, 2(2), 101-116; https://doi.org/10.3390/jdb2020101 - 11 Apr 2014
Cited by 34 | Viewed by 9626
Abstract
The epicardium is the mesothelial outer layer of the vertebrate heart. It plays an important role during cardiac development by, among other functions, nourishing the underlying myocardium, contributing to cardiac fibroblasts and giving rise to the coronary vasculature. The epicardium also exerts key [...] Read more.
The epicardium is the mesothelial outer layer of the vertebrate heart. It plays an important role during cardiac development by, among other functions, nourishing the underlying myocardium, contributing to cardiac fibroblasts and giving rise to the coronary vasculature. The epicardium also exerts key functions during injury responses in the adult and contributes to cardiac repair. In this article, we review current knowledge on the cellular and molecular mechanisms underlying epicardium formation in the zebrafish, a teleost fish, which is rapidly gaining status as an animal model in cardiovascular research, and compare it with the mechanisms described in other vertebrate models. We moreover describe the expression patterns of a subset of available zebrafish Wilms’ tumor 1 transgenic reporter lines and discuss their specificity, applicability and limitations in the study of epicardium formation. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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1323 KiB  
Article
Soluble VCAM-1 Alters Lipid Phosphatase Activity in Epicardial Mesothelial Cells: Implications for Lipid Signaling During Epicardial Formation
by Manjari Ranganathan, Danijela Dokic, Sonia W. Sterrett, Kathryn L. Dwyer and Robert W. Dettman
J. Dev. Biol. 2013, 1(2), 159-185; https://doi.org/10.3390/jdb1020159 - 18 Sep 2013
Viewed by 7620
Abstract
Epicardial formation involves the attachment of proepicardial (PE) cells to the heart and the superficial migration of mesothelial cells over the surface of the heart. Superficial migration has long been known to involve the interaction of integrins expressed by the epicardium and their [...] Read more.
Epicardial formation involves the attachment of proepicardial (PE) cells to the heart and the superficial migration of mesothelial cells over the surface of the heart. Superficial migration has long been known to involve the interaction of integrins expressed by the epicardium and their ligands expressed by the myocardium; however, little is understood about signals that maintain the mesothelium as it migrates. One signaling pathway known to regulate junctional contacts in epithelia is the PI3K/Akt signaling pathway and this pathway can be modified by integrins. Here, we tested the hypothesis that the myocardially expressed, integrin ligand VCAM-1 modulates the activity of the PI3K/Akt signaling pathway by activating the lipid phosphatase activity of PTEN. We found that epicardial cells stimulated with a soluble form of VCAM-1 (sVCAM-1) reorganized PTEN from the cytoplasm to the membrane and nucleus and activated PTEN’s lipid phosphatase activity. Chick embryonic epicardial mesothelial cells (EMCs) expressing a shRNA to PTEN increased invasion in collagen gels, but only after stimulation by TGFβ3, indicating that loss of PTEN is not sufficient to induce invasion. Expression of an activated form of PTEN was capable of blocking degradation of junctional complexes by TGFβ3. This suggested that PTEN plays a role in maintaining the mesothelial state of epicardium and not in EMT. We tested if altering PTEN activity could affect coronary vessel development and observed that embryonic chick hearts infected with a virus expressing activated human PTEN had fewer coronary vessels. Our data support a role for VCAM-1 in mediating critical steps in epicardial development through PTEN in epicardial cells. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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1221 KiB  
Review
Epicardial Origin of Resident Mesenchymal Stem Cells in the Adult Mammalian Heart
by Naisana S. Asli, Munira Xaymardan and Richard P. Harvey
J. Dev. Biol. 2014, 2(2), 117-137; https://doi.org/10.3390/jdb2020117 - 23 Apr 2014
Cited by 14 | Viewed by 9024
Abstract
The discovery of stem and progenitor cells in the adult mammalian heart has added a vital dimension to the field of cardiac regeneration. Cardiac-resident stem cells are likely sequestered as reserve cells within myocardial niches during the course of embryonic cardiogenesis, although they [...] Read more.
The discovery of stem and progenitor cells in the adult mammalian heart has added a vital dimension to the field of cardiac regeneration. Cardiac-resident stem cells are likely sequestered as reserve cells within myocardial niches during the course of embryonic cardiogenesis, although they may also be recruited from external sources, such as bone marrow. As we begin to understand the nature of cardiac-resident stem and progenitor cells using a variety of approaches, it is evident that they possess an identity embedded within their gene regulatory networks that favours cardiovascular lineage potential. In addition to contributing lineage descendants, cardiac stem cells may also be stress sensors, offering trophic cues to other cell types, including cardiomyocytes and vasculature cells, and likely other stem cells and immune cells, during adaptation and repair. This presents numerous possibilities for endogenous cardiac stem and progenitor cells to be used in cell therapies or as targets in heart rejuvenation. In this review, we focus on the epicardium as an endogenous source of multi-potential mesenchymal progenitor cells in development and as a latent source of such progenitors in the adult. We track the origin and plasticity of the epicardium in embryos and adults in both homeostasis and disease. In this context, we ask whether directed activation of epicardium-derived progenitor cells might have therapeutic application. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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255 KiB  
Review
Epicardium-Derived Heart Repair
by Anke M. Smits and Paul R. Riley
J. Dev. Biol. 2014, 2(2), 84-100; https://doi.org/10.3390/jdb2020084 - 10 Apr 2014
Cited by 20 | Viewed by 6557
Abstract
In the last decade, cell replacement therapy has emerged as a potential approach to treat patients suffering from myocardial infarction (MI). The transplantation or local stimulation of progenitor cells with the ability to form new cardiac tissue provides a novel strategy to overcome [...] Read more.
In the last decade, cell replacement therapy has emerged as a potential approach to treat patients suffering from myocardial infarction (MI). The transplantation or local stimulation of progenitor cells with the ability to form new cardiac tissue provides a novel strategy to overcome the massive loss of myocardium after MI. In this regard the epicardium, the outer layer of the heart, is a tractable local progenitor cell population for therapeutic pursuit. The epicardium has a crucial role in formation of the embryonic heart. After activation and migration into the developing myocardium, epicardial cells differentiate into several cardiac cells types. Additionally, the epicardium provides instructive signals for the growth of the myocardium and coronary angiogenesis. In the adult heart, the epicardium is quiescent, but recent evidence suggests that it becomes reactivated upon damage and recapitulates at least part of its embryonic functions. In this review we provide an update on the current knowledge regarding the contribution of epicardial cells to the adult mammalian heart during the injury response. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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1016 KiB  
Review
The Epicardium and the Development of the Atrioventricular Junction in the Murine Heart
by Marie M. Lockhart, Aimee L. Phelps, Maurice J. B. Van den Hoff and Andy Wessels
J. Dev. Biol. 2014, 2(1), 1-17; https://doi.org/10.3390/jdb2010001 - 04 Mar 2014
Cited by 30 | Viewed by 9418
Abstract
Insight into the role of the epicardium in cardiac development and regeneration has significantly improved over the past ten years. This is mainly due to the increasing availability of new mouse models for the study of the epicardial lineage. Here we focus on [...] Read more.
Insight into the role of the epicardium in cardiac development and regeneration has significantly improved over the past ten years. This is mainly due to the increasing availability of new mouse models for the study of the epicardial lineage. Here we focus on the growing understanding of the significance of the epicardium and epicardially-derived cells in the formation of the atrioventricular (AV) junction. First, through the process of epicardial epithelial-to-mesenchymal transformation (epiEMT), the subepicardial AV mesenchyme is formed. Subsequently, the AV-epicardium and epicardially-derived cells (EPDCs) form the annulus fibrosus, a structure important for the electrical separation of atrial and ventricular myocardium. Finally, the AV-EPDCs preferentially migrate into the parietal AV valve leaflets, largely replacing the endocardially-derived cell population. In this review, we provide an overview of what is currently known about the regulation of the events involved in this process. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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342 KiB  
Review
The Epicardium and Coronary Artery Formation
by Adriana A. S. Pires-Gomes and José M. Pérez-Pomares
J. Dev. Biol. 2013, 1(3), 186-202; https://doi.org/10.3390/jdb1030186 - 18 Oct 2013
Cited by 8 | Viewed by 8586
Abstract
The coronary system is the network of blood vessels that nourishes the heart muscle. After birth, proper coronary blood circulation is required to support heart homeostasis, and altered coronary function frequently leads to myocardial ischemia, infarction and heart failure. The epicardium plays a [...] Read more.
The coronary system is the network of blood vessels that nourishes the heart muscle. After birth, proper coronary blood circulation is required to support heart homeostasis, and altered coronary function frequently leads to myocardial ischemia, infarction and heart failure. The epicardium plays a pivotal role during coronary blood vessel embryonic development, contributing cells to the coronary vasculature, but also secreting diffusible signals that regulate coronary morphogenesis and secondarily impact on ventricular compact myocardium growth. Accordingly, anomalous epicardium development gives rise to the multiple congenital defects of the coronary vascular system and the heart walls. In this review, we will summarize and discuss our current knowledge on the embryogenesis of coronary blood vessels, as related to epicardial development, and attempt to highlight the biomedical relevance of this tissue. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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1106 KiB  
Review
Epicardial Lineages and Cardiac Repair
by Manvendra K. Singh and Jonathan A. Epstein
J. Dev. Biol. 2013, 1(2), 141-158; https://doi.org/10.3390/jdb1020141 - 26 Aug 2013
Cited by 6 | Viewed by 12540
Abstract
The death of cardiac myocytes resulting from myocardial infarction is a major cause of heart failure worldwide. Effective therapies for regenerating lost cardiac myocytes are lacking. Recently, the epicardium has been implicated as a source of inflammatory cytokines, growth factors and progenitor cells [...] Read more.
The death of cardiac myocytes resulting from myocardial infarction is a major cause of heart failure worldwide. Effective therapies for regenerating lost cardiac myocytes are lacking. Recently, the epicardium has been implicated as a source of inflammatory cytokines, growth factors and progenitor cells that modulate the response to myocardial injury. During embryonic development, epicardially-derived cells have the potential to differentiate into multiple cardiac lineages, including fibroblasts, vascular smooth muscle and potentially other cell types. In the healthy adult heart, epicardial cells are thought to be generally quiescent. However, injury of the adult heart results in reactivation of a developmental gene program in the epicardium, which leads to increased epicardial cell proliferation and differentiation of epicardium-derived cells (EPDCs) into various cardiac lineages. Recent work suggests that epicardial reactivation after injury is accompanied by, and contributes to, a robust inflammatory response. In this review, we describe the current status of research related to epicardial biology in cardiac development and regeneration, highlighting important recent discoveries and ongoing controversies. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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295 KiB  
Review
Left-Right Asymmetrical Development of the Proepicardium
by Jan Schlueter and Thomas Brand
J. Dev. Biol. 2013, 1(2), 126-140; https://doi.org/10.3390/jdb1020126 - 26 Jul 2013
Cited by 1 | Viewed by 7961
Abstract
The proepicardium (PE) is a cluster of cells that forms on the cardiac inflow tract and gives rise to the epicardium and connective tissue and largely contributes to the coronary vasculature. In many vertebrates, the PE undergoes left-right asymmetrical development. While PE cells [...] Read more.
The proepicardium (PE) is a cluster of cells that forms on the cardiac inflow tract and gives rise to the epicardium and connective tissue and largely contributes to the coronary vasculature. In many vertebrates, the PE undergoes left-right asymmetrical development. While PE cells and marker genes can be initially found on both sides, only the right-sided PE will fully develop and ultimately deliver cells to the heart. Several signalling inputs, like FGF and BMP signals, are involved in PE induction in the lateral plate mesoderm, as well as during inflow tract formation and, also, control asymmetric PE development. These signalling events will be put into the context of embryonic left-right asymmetry determination. Finally, it will be discussed whether PE development may serve as a readout for asymmetric inflow tract morphogenesis. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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184 KiB  
Review
Epicardium Formation as a Sensor in Toxicology
by Peter Hofsteen, Jessica Plavicki, Richard E. Peterson and Warren Heideman
J. Dev. Biol. 2013, 1(2), 112-125; https://doi.org/10.3390/jdb1020112 - 24 Jul 2013
Cited by 1 | Viewed by 6435
Abstract
Zebrafish (Danio rerio) are an excellent vertebrate model for studying heart development, regeneration and cardiotoxicity. Zebrafish embryos exposed during the temporal window of epicardium development to the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit severe heart malformations. TCDD exposure [...] Read more.
Zebrafish (Danio rerio) are an excellent vertebrate model for studying heart development, regeneration and cardiotoxicity. Zebrafish embryos exposed during the temporal window of epicardium development to the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit severe heart malformations. TCDD exposure prevents both proepicardial organ (PE) and epicardium development. Exposure later in development, after the epicardium has formed, does not produce cardiac toxicity. It is not until the adult zebrafish heart is stimulated to regenerate does TCDD again cause detrimental effects. TCDD exposure prior to ventricular resection prevents cardiac regeneration. It is likely that TCDD-induced inhibition of epicardium development and cardiac regeneration occur via a common mechanism. Here, we describe experiments that focus on the epicardium as a target and sensor of zebrafish heart toxicity. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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366 KiB  
Review
Transcriptional Control of Cell Lineage Development in Epicardium-Derived Cells
by Caitlin M. Braitsch and Katherine E. Yutzey
J. Dev. Biol. 2013, 1(2), 92-111; https://doi.org/10.3390/jdb1020092 - 03 Jul 2013
Cited by 35 | Viewed by 11367
Abstract
Epicardial derivatives, including vascular smooth muscle cells and cardiac fibroblasts, are crucial for proper development of the coronary vasculature and cardiac fibrous matrix, both of which support myocardial integrity and function in the normal heart. Epicardial formation, epithelial-to-mesenchymal transition (EMT), and epicardium-derived cell [...] Read more.
Epicardial derivatives, including vascular smooth muscle cells and cardiac fibroblasts, are crucial for proper development of the coronary vasculature and cardiac fibrous matrix, both of which support myocardial integrity and function in the normal heart. Epicardial formation, epithelial-to-mesenchymal transition (EMT), and epicardium-derived cell (EPDC) differentiation are precisely regulated by complex interactions among signaling molecules and transcription factors. Here we review the roles of critical transcription factors that are required for specific aspects of epicardial development, EMT, and EPDC lineage specification in development and disease. Epicardial cells and subepicardial EPDCs express transcription factors including Wt1, Tcf21, Tbx18, and Nfatc1. As EPDCs invade the myocardium, epicardial progenitor transcription factors such as Wt1 are downregulated. EPDC differentiation into SMC and fibroblast lineages is precisely regulated by a complex network of transcription factors, including Tcf21 and Tbx18. These and other transcription factors also regulate epicardial EMT, EPDC invasion, and lineage maturation. In addition, there is increasing evidence that epicardial transcription factors are reactivated with adult cardiac ischemic injury. Determining the function of reactivated epicardial cells in myocardial infarction and fibrosis may improve our understanding of the pathogenesis of heart disease. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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327 KiB  
Review
Induction of the Proepicardium
by Lisandro Maya-Ramos, James Cleland, Michael Bressan and Takashi Mikawa
J. Dev. Biol. 2013, 1(2), 82-91; https://doi.org/10.3390/jdb1020082 - 01 Jul 2013
Cited by 27 | Viewed by 7730
Abstract
The proepicardium is a transient extracardiac embryonic tissue that gives rise to the epicardium and a number of coronary vascular cell lineages. This important extracardiac tissue develops through multiple steps of inductive events, from specification of multiple cell lineages to morphogenesis. This article [...] Read more.
The proepicardium is a transient extracardiac embryonic tissue that gives rise to the epicardium and a number of coronary vascular cell lineages. This important extracardiac tissue develops through multiple steps of inductive events, from specification of multiple cell lineages to morphogenesis. This article will review our current understanding of inductive events involved in patterning of the proepicardium precursor field, specification of cell types within the proepicardium and their extension and attachment to the heart. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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1068 KiB  
Review
Development of the Serosal Mesothelium
by Nichelle I. Winters and David M. Bader
J. Dev. Biol. 2013, 1(2), 64-81; https://doi.org/10.3390/jdb1020064 - 26 Jun 2013
Cited by 17 | Viewed by 21607
Abstract
Mesothelia in the adult vertebrate are the simple squamous epithelia covering all coelomic organs and body cavities. Until recently, analysis of the generation and differentiative potential of mesothelia in organogenesis has largely focused on development of visceral mesothelium of the heart; the epicardium [...] Read more.
Mesothelia in the adult vertebrate are the simple squamous epithelia covering all coelomic organs and body cavities. Until recently, analysis of the generation and differentiative potential of mesothelia in organogenesis has largely focused on development of visceral mesothelium of the heart; the epicardium and its progenitor, the proepicardium. Here, we review emerging data on the development and differentiation of serosal mesothelium, the covering of the gastrointestinal tract. This literature demonstrates that serosal mesothelium is generated through a completely different mechanism than that seen in the heart suggesting that commitment of progenitors to this cell lineage does not follow a common pathway. The differentiative potential of serosal mesothelium is also discussed in comparison to that observed for progeny of the proepicardium/epicardium. In our review of the literature, we point out gaps in our understanding of serosal mesothelial development and that of mesothelial development as a whole. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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879 KiB  
Review
Microsurgical Procedures for Studying the Developmental Significance of the Proepicardium and Epicardium in Avian Embryos: PE-Blocking, PE-Photoablation, and PE-Grafting
by Jörg Männer
J. Dev. Biol. 2013, 1(1), 47-63; https://doi.org/10.3390/jdb1010047 - 21 Jun 2013
Cited by 3 | Viewed by 8386
Abstract
The epicardium is the outer skin of the mature vertebrate heart. Its embryonic origin and its possible roles in the developing and mature heart did not receive much recognition during the 19th and most of the 20th century. During the past 25 years, [...] Read more.
The epicardium is the outer skin of the mature vertebrate heart. Its embryonic origin and its possible roles in the developing and mature heart did not receive much recognition during the 19th and most of the 20th century. During the past 25 years, however, the epicardium came into the focus of developmental biology and regenerative medicine. Clinical researchers usually prefer genetically modified mouse models when they want to gain insight into developmental or pathological processes. The story of research on the embryonic epicardium, however, nicely demonstrates the value of non-mammalian species, namely avian species, for elucidating fundamental processes in embryonic and fetal development. Studies on chick and quail embryos have not only led to the identification of the primarily extracardiac source of the epicardium—presently called the proepicardium (PE)—they have also significantly contributed to our current knowledge about the developmental significance of the embryonic epicardium. In this review article, I describe three “classical” microsurgical experiments that have been developed for studying the developmental significance of the PE/epicardium in avian embryos (mechanical PE-blocking, PE-photoablation, orthotopic PE-grafting). Furthermore, I show how these microsurgical experiments have contributed to our current knowledge about the roles of the PE/epicardium in cardiac development. There are still some unsolved aspects in the physiology of the developing epicardium, which may be clarified with the aid of these “classical” microsurgical experiments. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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757 KiB  
Review
Role of Prokineticin Receptor-1 in Epicardial Progenitor Cells
by Thu Lan Nguyen, Adelin Gasser and Canan G. Nebigil
J. Dev. Biol. 2013, 1(1), 20-31; https://doi.org/10.3390/jdb1010020 - 18 Jun 2013
Cited by 8 | Viewed by 8661 | Correction
Abstract
G protein-coupled receptors (GPCRs) form a large class of seven transmembrane (TM) domain receptors. The use of endogenous GPCR ligands to activate the stem cell maintenance or to direct cell differentiation would overcome many of the problems currently encountered in the use of [...] Read more.
G protein-coupled receptors (GPCRs) form a large class of seven transmembrane (TM) domain receptors. The use of endogenous GPCR ligands to activate the stem cell maintenance or to direct cell differentiation would overcome many of the problems currently encountered in the use of stem cells, such as rapid in vitro differentiation and expansion or rejection in clinical applications. This review focuses on the definition of a new GPCR signaling pathway activated by peptide hormones, called “prokineticins”, in epicardium-derived cells (EPDCs). Signaling via prokineticin-2 and its receptor, PKR1, is required for cardiomyocyte survival during hypoxic stress. The binding of prokineticin-2 to PKR1 induces proliferation, migration and angiogenesis in endothelial cells. The expression of prokineticin and PKR1 increases during cardiac remodeling after myocardial infarction. Gain of function of PKR1 in the adult mouse heart revealed that cardiomyocyte-PKR1 signaling activates EPDCs in a paracrine fashion, thereby promoting de novo vasculogenesis. Transient PKR1 gene therapy after myocardial infarction in mice decreases mortality and improves heart function by promoting neovascularization, protecting cardiomyocytes and mobilizing WT1+ cells. Furthermore, PKR1 signaling promotes adult EPDC proliferation and differentiation to adopt endothelial and smooth muscle cell fate, for the induction of de novo vasculogenesis. PKR1 is expressed in the proepicardium and epicardial cells derived from mice kidneys. Loss of PKR1 causes deficits in EPDCs in the neonatal mice hearts and kidneys and impairs vascularization and heart and kidney function. Taken together, these data indicate a novel role for PKR1 in heart-kidney complex via EPDCs. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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992 KiB  
Review
Evolutionary Origin of the Proepicardium
by Elena Cano, Rita Carmona and Ramón Muñoz-Chápuli
J. Dev. Biol. 2013, 1(1), 3-19; https://doi.org/10.3390/jdb1010003 - 30 May 2013
Cited by 4 | Viewed by 8870
Abstract
The embryonic epicardium and the cardiac mesenchyme derived from it are critical to heart development. The embryonic epicardium arises from an extracardiac progenitor tissue called the proepicardium, a proliferation of coelomic cells located at the limit between the liver and the sinus venosus. [...] Read more.
The embryonic epicardium and the cardiac mesenchyme derived from it are critical to heart development. The embryonic epicardium arises from an extracardiac progenitor tissue called the proepicardium, a proliferation of coelomic cells located at the limit between the liver and the sinus venosus. A proepicardium has not been described in invertebrates, and the evolutionary origin of this structure in vertebrates is unknown. We herein suggest that the proepicardium might be regarded as an evolutionary derivative from an ancient pronephric external glomerulus that has lost its excretory role. In fact, we previously described that the epicardium arises by cell migration from the primordia of the right pronephric external glomerulus in a representative of the most primitive vertebrate lineage, the lamprey Petromyzon marinus. In this review, we emphasize the striking similarities between the gene expression profiles of the proepicardium and the developing kidneys, as well as the parallelisms in the signaling mechanisms involved in both cases. We show some preliminary evidence about the existence of an inhibitory mechanism blocking glomerular differentiation in the proepicardium. We speculate as to the possibility that this developmental link between heart and kidney can be revealing a phylogenetically deeper association, supported by the existence of a heart-kidney complex in Hemichordates. Finally, we suggest that primitive hematopoiesis could be related with this heart-kidney complex, thus accounting for the current anatomical association of the hematopoietic stem cells with an aorta-gonad-mesonephros area. In summary, we think that our hypothesis can provide new perspectives on the evolutionary origin of the vertebrate heart. Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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2 pages, 307 KiB  
Correction
Correction: Nguyen T.L., et al. Role of Prokineticin Receptor-1 in Epicardial Progenitor Cells. J. Dev. Biol. 2013, 1, 20–31
by Thu Lan Nguyen, Adeline Gasser and Canan G. Nebigil
J. Dev. Biol. 2020, 8(4), 32; https://doi.org/10.3390/jdb8040032 - 11 Dec 2020
Cited by 1 | Viewed by 1711
Abstract
The authors wish to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue Epicardial Development and Cardiovascular Disease)
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