Journal of Developmental Biology

1323 KiB

Open AccessArticle

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

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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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1106 KiB

Open AccessReview

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 7 | Viewed by 13036

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

Open AccessReview

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 8282

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

Open AccessReview

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 2 | Viewed by 6765

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

Open AccessReview

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 - 3 Jul 2013

Cited by 35 | Viewed by 11858

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

Open AccessReview

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 - 1 Jul 2013

Cited by 28 | Viewed by 8071

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

Open AccessReview

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 23043

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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J. Dev. Biol., Volume 1, Issue 2 (September 2013) – 7 articles , Pages 64-185

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