23 results on '"Iriarte, M."'
Search Results
2. Epithelial‐mesenchymal Transition and Cancer Stem Cells: At the Crossroads of Differentiation and Dedifferentiation.
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Wang, Hanmin and Unternaehrer, Juli J.
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In this review, we explore the connections between epithelial‐mesenchymal transition (EMT) and differentiation status. EMTs in development have been described as differentiation events, while in most cases EMTs in cancer have been depicted as dedifferentiation events. We will briefly summarize both embryo development and cancer progression with regard to the involvement of EMT and cell differentiation status. We further present the studies that provide evidence that EMT results in both differentiation and dedifferentiation. Finally, we present our resolution to this dilemma by suggesting that EMT brings about dedifferentiation that enables subsequent differentiation. In normal development, EMT events may cause a partial reversal of differentiation to overcome differentiation barriers. When EMT is aberrantly activated in cancer, cells gain attributes of stem cells that contribute to self‐renewal capabilities and are able to differentiate to all cell types represented in the tumor. The resulting cancer stem cells attain hallmarks of cancer, including replicative immortality, resistance to cell death, and invasiveness. Developmental Dynamics 248:10–20, 2019. © 2018 Wiley Periodicals, Inc. Key Findings: Overview of epitehlial‐mesenchyaml transition (EMT) in both embryo development and cancer progression.Exploring the connection between cell stemness to its EMT status.Reviewing the current dilemma of either EMT results in differentiation or dedifferentiation 4. Providing a novel resolution. [ABSTRACT FROM AUTHOR]
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- 2019
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3. CCBE1 is required for coronary vessel development and proper coronary artery stem formation in the mouse heart.
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Bonet, Fernando, Pereira, Paulo N. G., Bover, Oriol, Marques, Sara, Inácio, José M., and Belo, José A.
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Background: Proper coronary vasculature development is essential for late‐embryonic and adult heart function. The developmental regulation of coronary embryogenesis is complex and includes the coordinated activity of multiple signaling pathways. CCBE1 plays an important role during lymphangiogenesis, enhancing VEGF‐C signaling, which is also required for coronary vasculature formation. However, whether CCBE1 plays a similar role during coronary vasculature development is still unknown. Here, we investigate the coronary vasculature development in Ccbe1 mutant embryos. Results: We show that Ccbe1 is expressed in the epicardium, like Vegf‐c, and also in the sinus venosus (SV) at the stages of its contribution to coronary vasculature formation. We also report that absence of CCBE1 in cardiac tissue inhibited coronary growth that sprouts from the SV endocardium at the dorsal cardiac wall. This disruption of coronary formation correlates with abnormal processing of VEGF‐C propeptides, suggesting VEGF‐C–dependent signaling alteration. Moreover, Ccbe1 loss‐of‐function leads to the development of defective dorsal and ventral intramyocardial vessels. We also demonstrate that Ccbe1 mutants display delayed and mispatterned coronary artery (CA) stem formation. Conclusions: CCBE1 is essential for coronary vessel formation, independent of their embryonic origin, and is also necessary for peritruncal vessel growth and proper CA stem patterning. Developmental Dynamics 247:1135‐1145, 2018. © 2018 Wiley Periodicals, Inc. Key Findings: Ccbe1 is expressed in the epicardium and sinus venosus (SV) myocardium during coronary vasculature development.CCBE1 is required for SV endocardium‐derived coronary vessel development enhancing VEGF‐C processing.CCBE1 is required for the development of the coronary vessels forming at the ventral cardiac side of the heart.CCBE1 is necessary for peritruncal vessel growth and proper coronary artery (CA) stem formation. [ABSTRACT FROM AUTHOR]
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- 2018
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4. Alterations in retinoic acid signaling affect the development of the mouse coronary vasculature.
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Wang, Suya, Huang, Weiliang, Castillo, Hozana A., Kane, Maureen A., Xavier‐Neto, José, Trainor, Paul A., and Moise, Alexander R.
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Background: During the final stages of heart development the myocardium grows and becomes vascularized by means of paracrine factors and cell progenitors derived from the epicardium. There is evidence to suggest that retinoic acid (RA), a metabolite of vitamin A, plays an important role in epicardial‐based developmental programming. However, the consequences of altered RA‐signaling in coronary development have not been systematically investigated. Results: We explored the developmental consequences of altered RA‐signaling in late cardiogenic events that involve the epicardium. For this, we used a model of embryonic RA excess based on mouse embryos deficient in the retinaldehyde reductase DHRS3, and a complementary model of embryonic RA deficiency based on pharmacological inhibition of RA synthesis. We found that alterations in embryonic RA signaling led to a thin myocardium and aberrant coronary vessel formation and remodeling. Both excess, and deficient RA‐signaling are associated with reductions in ventricular coverage and density of coronary vessels, altered vessel morphology, and impaired recruitment of epicardial‐derived mural cells. Using a combined transcriptome and proteome profiling approach, we found that RA treatment of epicardial cells influenced key signaling pathways relevant for cardiac development. Conclusions: Epicardial RA‐signaling plays critical roles in the development of the coronary vasculature needed to support myocardial growth. Developmental Dynamics 247:976‐991, 2018. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
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- 2018
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5. Avian embryonic coronary arterio‐venous patterning involves the contribution of different endothelial and endocardial cell populations.
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Palmquist‐Gomes, Paul, Guadix, Juan Antonio, and Pérez‐Pomares, José M.
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Background: Coronary vasculature irrigates the myocardium and is crucial to late embryonic and adult heart function. Despite the developmental significance and clinical relevance of these blood vessels, the embryonic origin and the cellular and molecular mechanisms that regulate coronary arterio‐venous patterning are not known in detail. In this study, we have used the avian embryo to dissect the ontogenetic origin and morphogenesis of coronary vasculature.Results: We show that sinus venosus endocardial sprouts and proepicardial angioblasts pioneer coronary vascular formation, invading the developing heart simultaneously. We also report that avian ventricular endocardium has the potential to contribute to coronary vessels, and describe the incorporation of cardiac distal outflow tract endothelial cells to the peritruncal endothelial plexus to participate in coronary vascular formation. Finally, our findings indicate that large sinus venosus‐independent sections of the forming coronary vasculature develop without connection to the systemic circulation and that coronary arterio‐venous shunts form a few hours before peritruncal arterial endothelium connects to the aortic root.Conclusions: Embryonic coronary vasculature is a developmental mosaic, formed by the integration of vascular cells from, at least, four different embryological origins, which assemble in a coordinated manner to complete coronary vascular development.Developmental Dynamics 247:686–698, 2018 . © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]- Published
- 2018
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6. Coronary stem development in wild-type and Tbx1 null mouse hearts.
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Théveniau‐Ruissy, Magali, Pérez‐Pomares, José‐Maria, Parisot, Pauline, Baldini, Antonio, Miquerol, Lucile, and Kelly, Robert G.
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Background: Coronary artery (CA) stems connect the ventricular coronary tree with the aorta. Defects in proximal CA patterning are a cause of sudden cardiac death. In mice lacking Tbx1, common arterial trunk is associated with an abnormal trajectory of the proximal left CA. Here we investigate CA stem development in wild-type and Tbx1 null embryos. Results: Genetic lineage tracing reveals that limited outgrowth of aortic endothelium contributes to proximal CA stems. Immunohistochemistry and fluorescent tracer injections identify a periarterial vascular plexus present at the onset of CA stem development. Transplantation experiments in avian embryos indicate that the periarterial plexus originates in mesenchyme distal to the outflow tract. Tbx1 is required for the patterning but not timing of CA stem development and a Tbx1 reporter allele is expressed in myocardium adjacent to the left but not right CA stem. This expression domain is maintained in Sema3c
−/− hearts with a common arterial trunk and leftward positioned CA. Ectopic myocardial differentiation is observed on the left side of the Tbx1−/− common arterial trunk. Conclusions: A periarterial plexus bridges limited outgrowth of the aortic endothelium with the ventricular plexus during CA stem development. Molecular differences associated with left and right CA stems provide new insights into the etiology of CA patterning defects. Developmental Dynamics 245:445-459, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]- Published
- 2016
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7. Wnt signaling in the heart fields: Variations on a common theme.
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Ruiz ‐ Villalba, Adrián, Hoppler, Stefan, and van den Hoff, Maurice J.B.
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Wnt signaling plays an essential role in development and differentiation. Heart development is initiated with the induction of precardiac mesoderm requiring the tightly and spatially controlled regulation of canonical and noncanonical Wnt signaling pathways. The role of Wnt signaling in subsequent development of the heart fields is to a large extent unclear. We will discuss the role of Wnt signaling in the development of the arterial and venous pole of the heart, highlighting the dual roles of Wnt signaling with respect to its time- and dosage-dependent effects and the balance between the canonical and noncanonical signaling. Canonical signaling appears to be involved in retaining the cardiac precursors in a proliferative and precursor state, whereas noncanonical signaling promotes their differentiation. Thereafter, both canonical and noncanonical signaling regulate specific steps in differentiation of the cardiac compartments. Because heart development is a contiguous, rather than a sequential, process, analyses tend only to show a single timeframe of development. The repetitive alternating and reciprocal effect of canonical and noncanonical signaling is lost when studied in homogenates. Without the simultaneous in vivo visualization of the different Wnt signaling pathways, the mechanism of Wnt signaling in heart development remains elusive. Developmental Dynamics 245:294-306, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
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- 2016
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8. Coelomic epithelium-derived cells in visceral morphogenesis.
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Ariza, Laura, Carmona, Rita, Cañete, Ana, Cano, Elena, and Muñoz ‐ Chápuli, Ramón
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Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans. Developmental Dynamics 245:307-322, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
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- 2016
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9. The chick embryo as an expanding experimental model for cancer and cardiovascular research.
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Kain, Kristin H., Miller, James W.I., Jones‐Paris, Celestial R., Thomason, Rebecca T., Lewis, John D., Bader, David M., Barnett, Joey V., and Zijlstra, Andries
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A long and productive history in biomedical research defines the chick as a model for human biology. Fundamental discoveries, including the description of directional circulation propelled by the heart and the link between oncogenes and the formation of cancer, indicate its utility in cardiac biology and cancer. Despite the more recent arrival of several vertebrate and invertebrate animal models during the last century, the chick embryo remains a commonly used model for vertebrate biology and provides a tractable biological template. With new molecular and genetic tools applied to the avian genome, the chick embryo is accelerating the discovery of normal development and elusive disease processes. Moreover, progress in imaging and chick culture technologies is advancing real-time visualization of dynamic biological events, such as tissue morphogenesis, angiogenesis, and cancer metastasis. A rich background of information, coupled with new technologies and relative ease of maintenance, suggest an expanding utility for the chick embryo in cardiac biology and cancer research. Developmental Dynamics 243:216-228, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
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- 2014
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10. Comprehensive timeline of mesodermal development in the quail small intestine.
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Thomason, Rebecca T., Bader, David M., and Winters, Nichelle I.
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Background: To generate the mature intestine, splanchnic mesoderm diversifies into six different tissue layers each with multiple cell types through concurrent and complex morphogenetic events. Hindering the progress of research in the field is the lack of a detailed description of the fundamental morphological changes that constitute development of the intestinal mesoderm. Results: We used immunofluorescence and morphometric analyses of wild-type and Tg( tie1:H2B-eYFP) quail embryos to establish a comprehensive timeline of mesodermal development in the avian intestine. The following landmark features were analyzed from appearance of the intestinal primordium through generation of the definitive structure: radial compartment formation, basement membrane dynamics, mesothelial differentiation, mesenchymal expansion and growth patterns, smooth muscle differentiation, and maturation of the vasculature. In this way, structural relationships between mesodermal components were identified over time. Conclusions: This integrated analysis presents a roadmap for investigators and clinicians to evaluate diverse experimental data obtained at individual stages of intestinal development within the longitudinal context of intestinal morphogenesis. Developmental Dynamics 241:1678-1694, 2012. © 2012 Wiley Periodicals,Inc. [ABSTRACT FROM AUTHOR]
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- 2012
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11. Cellular phenotypes and spatio-temporal patterns of lymphatic vessel development in embryonic mouse hearts.
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Flaht, A., Jankowska-Steifer, E., Radomska, D.M., Madej, M., Gula, G., Kujawa, M., and Ratajska, A.
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Background: The origin of cardiac lymphatics from venous endothelial cells or from scattered lymphangioblasts has been discussed in the literature. We aimed to establish the stage when lymphatic vessels appear in the developing mouse heart, the location of the first lymphatics, and to define cellular phenotypes of growing lymphatics. Results: We found that scattered Lyve-1-positive cells located in the subepicardial area of developing heart expressed CD45, CD68, F4/80, or CD11b but not CD31. Prox-1
+ /Lyve-1+ cellular cords or vessels were found to invade 12.5-13.5-dpc hearts via two routes: from the venous pole, i.e., dorsal atrioventricular sulcus, or on the dorsal atrial surface from mediastinum and from the arterial pole, i.e., along the great arteries. The Prox-1+ /Lyve-1+ vessels were located among the Prox-1+ /Lyve-1− cords and among the scattered Prox-1− /Lyve-1+ cells. The Prox-1+ /Lyve-1− cellular cords/tubules dominate initially at the arterial pole whereas Lyve-1+ /Prox-1− cellular cords/tubules dominate initially on the venous pole, i.e., dorsal atrioventricular sulcus. The Lyve-1+ /CD45+ , Lyve-1+ /CD11b+ , Lyve-1+ /F4/80+ and Lyve-1+ /CD68+ cells were subsequently found to be co-opted to the wall of the developing lymphatic vessels while gaining Flk-1. Conclusions: Lymphatic primordia exhibit different cellular phenotypes and different spatiotemporal pattern on the venous pole as compared with the arterial pole of the heart. Developmental Dynamics 241:1473-1486, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]- Published
- 2012
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12. The identification of different endothelial cell populations within the mouse proepicardium.
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Cossette, Stephanie and Misra, Ravi
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The proepicardium is a transient embryonic structure that is a source of precursors of the epicardium, coronary smooth muscle cells, and may be a source of coronary endothelial cells (EC). To better understand proepicardium development a systematic analysis of EC appearance was performed. Multiple marker analysis showed that EC are present in the mouse proepicardium at embryonic day (E) 9.0 through E9.75. Distinct populations of EC were found that were associated with the liver bud, and the sinus venosus, as well as a population that do not appear to be associated with either of these structures. There was a temporal increase in the number of EC and temporal changes in the distribution of EC within the different populations during PE development. These findings indicate that EC exist in the proepicardium before coronary vasculogenesis, and support a model in which there is a heterogeneous origin for EC in the proepicardium. Developmental Dynamics 240:2344-2353, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2011
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13. Expression of the familial cardiac valvular dystrophy gene, filamin-A, during heart morphogenesis.
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Norris, R.A., Moreno-Rodriguez, R., Wessels, A., Merot, J., Bruneval, P., Chester, A.H., Yacoub, M.H., Hagège, A., Slaugenhaupt, S.A., Aikawa, E., Schott, J.J., Lardeux, A., Harris, B.S., Williams, L.K., Richards, A., Levine, R.A., and Markwald, R.R.
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Myxoid degeneration of the cardiac valves is a common feature in a heterogeneous group of disorders that includes Marfan syndrome and isolated valvular diseases. Mitral valve prolapse is the most common outcome of these and remains one of the most common indications for valvular surgery. While the etiology of the disease is unknown, recent genetic studies have demonstrated that an X-linked form of familial cardiac valvular dystrophy can be attributed to mutations in the Filamin-A gene. Since these inheritable mutations are present from conception, we hypothesize that filamin-A mutations present at the time of valve morphogenesis lead to dysfunction that progresses postnatally to clinically relevant disease. Therefore, by carefully evaluating genetic factors (such as filamin-A) that play a substantial role in MVP, we can elucidate relevant developmental pathways that contribute to its pathogenesis. In order to understand how developmental expression of a mutant protein can lead to valve disease, the spatio-temporal distribution of filamin-A during cardiac morphogenesis must first be characterized. Although previously thought of as a ubiquitously expressed gene, we demonstrate that filamin-A is robustly expressed in non-myocyte cells throughout cardiac morphogenesis including epicardial and endocardial cells, and mesenchymal cells derived by EMT from these two epithelia, as well as mesenchyme of neural crest origin. In postnatal hearts, expression of filamin-A is significantly decreased in the atrioventricular and outflow tract valve leaflets and their suspensory apparatus. Characterization of the temporal and spatial expression pattern of filamin-A during cardiac morphogenesis is a crucial first step in our understanding of how mutations in filamin-A result in clinically relevant valve disease. Developmental Dynamics 239:2118-2127, 2010 © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2010
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14. A migratory role for EphrinB ligands in avian epicardial mesothelial cells.
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Wengerhoff, Sonia M., Weiss, Amy R., Dwyer, Kathryn L., and Dettman, Robert W.
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Little is known about the molecules that mediate the attachment of proepicardial cells to the heart. Ephrins are cell surface ligands for Eph tyrosine kinase receptors, molecules known to play a role in cell adhesion and migration. Here, we detected EphrinB ligands in proepicardial and epicardial mesothelial cells (EMCs) using reverse transcriptase-polymerase chain reaction, immunoblotting, immunolocalization, and EphB-Fc binding. Aggregated EphB-Fc fragments clustered ephrinB1 ligands on living EMCs indicating that they are cell surface expressed. In vitro assays demonstrated that ephrinB ligands participate in EMC migration but not cell adhesion. Localization studies in hearts at Hamburger and Hamilton stage 30 and older revealed that ephrinB1 is expressed in the epicardium and subepicardial mesenchyme of the atrioventricular sulcus. EMCs treated with platelet-derived growth factor-BB expressed smooth muscle markers but not ephrinB1. Our study supports an early role for ephrinB ligands for migration of epicardial cells and a later role in perivascular fibroblasts of coronary vessels in the atrioventricular sulcus. Developmental Dynamics 239:598-609, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2010
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15. Platelet-derived growth factor is involved in the differentiation of second heart field-derived cardiac structures in chicken embryos.
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Bax, Noortje A.M., Lie-Venema, Heleen, Vicente-Steijn, Rebecca, Bleyl, Steven B., Van Den Akker, Nynke M.S., Maas, Saskia, Poelmann, Robert E., and Gittenberger-de Groot, Adriana C.
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For the establishment of a fully functional septated heart, addition of myocardium from second heart field-derived structures is important. Platelet-derived growth factors (PDGFs) are known for their role in cardiovascular development. In this study, we aim to elucidate this role of PDGF-A, PDGF-C, and their receptor PDGFR-α. We analyzed the expression patterns of PDGF-A, -C, and their receptor PDGFR-α during avian heart development. A spatiotemporal pattern of ligands was seen with colocalization of the PDGFR-α. This was found in second heart field-derived myocardium as well as the proepicardial organ (PEO) and epicardium. Mechanical inhibition of epicardial outgrowth as well as chemical disturbance of PDGFR-α support a functional role of the ligands and the receptor in cardiac development. Developmental Dynamics 238:2658-2669, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2009
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16. Remodeling of aortic smooth muscle during avian embryonic development.
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Wiegreffe, Christoph, Christ, Bodo, Huang, Ruijin, and Scaal, Martin
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The dorsal aorta is the earliest formed intraembryonic blood vessel in vertebrates composed of an inner lining of endothelial cells (ECs) and a slightly later-forming outer wall consisting of vascular smooth muscle cells (SMCs) and pericytes. We previously identified the sclerotome as the only somitic compartment contributing to aortic SMCs in the trunk of the avian embryo. However, we demonstrated that the first SMCs in the aortic floor are not of somitic origin and must be derived from a different source. Here, we show that the primary SMCs are a transient population of aortic wall cells originating from the splanchnic mesoderm. A model is presented suggesting that wall formation of the early dorsal aorta in chick is a two-step process: The primary, transient SMCs in the aortic floor originate in the splanchnic mesoderm, whereas the secondary, definitive SMCs of the entire aortic wall originate in the sclerotome. Developmental Dynamics 238:624-631, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2009
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17. Coronary endothelial proliferation and morphogenesis are regulated by a VEGF-mediated pathway.
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Nesbitt, Tresa L., Roberts, Andrea, Tan, Hong, Junor, Lorain, Yost, Michael J., Potts, Jay D., Dettman, Robert W., and Goodwin, Richard L.
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Though development of the coronary vasculature is a critical event during embryogenesis, the molecular mechanisms that regulate its formation are not well characterized. Two unique approaches were used to investigate interactions between cardiac myocytes and proepicardial (PE) cells, which are the coronary anlagen. One of these experimental approaches used a 3-D collagen scaffold system on which specific cell-cell and cell-matrix interactions were studied. The other approach used a whole heart culture system that allowed for the analysis of epicardial to mesenchymal transformation (EMT). The VEGF signaling system has been implicated previously as an important regulator of coronary development. Our results demonstrated that a specific isoform of VEGF-A, VEGF, increased PE-derived endothelial cell proliferation and also increased EMT. However, VEGF-stimulated endothelial cells did not robustly coalesce into endothelial tubes as they did when cocultured with cardiac myocytes. Interestingly, blocking VEGF signaling via flk-1 inhibition reduced endothelial tube formation despite the presence of cardiac myocytes. These results indicate that VEGF signaling is complex during coronary development and that combinatorial signaling by other VEGF-A isoforms or other flk-1-binding VEGFs are likely to regulate endothelial tube formation. Developmental Dynamics 238:423-430, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2009
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18. Origin and fate of cardiac mesenchyme.
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Snarr, Brian S., Kern, Christine B., and Wessels, Andy
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The development of the embryonic heart is dependent upon the generation and incorporation of different mesenchymal subpopulations that derive from intra- and extra-cardiac sources, including the endocardium, epicardium, neural crest, and second heart field. Each of these populations plays a crucial role in cardiovascular development, in particular in the formation of the valvuloseptal apparatus. Notwithstanding shared mechanisms by which these cells are generated, their fate and function differ profoundly by their originating source. While most of our early insights into the origin and fate of the cardiac mesenchyme has come from experimental studies in avian model systems, recent advances in transgenic mouse technology has enhanced our ability to study these cell populations in the mammalian heart. In this article, we will review the current understanding of the role of cardiac mesenchyme in cardiac morphogenesis and discuss several new paradigms based on recent studies in the mouse. Developmental Dynamics 237:2804-2819, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2008
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19. Development of lymphatic vessels in mouse embryonic and early postnatal hearts.
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Juszyński, Michał, Ciszek, Bogdan, Stachurska, Emilia, Jabłońska, Anna, and Ratajska, Anna
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We aimed to study the spatiotemporal pattern of lymphatic system formation in the embryonic and early postnatal mouse hearts. The first sign of the development of lymphatics are Lyve-1-positive cells located on the subepicardial area. Strands of Lyve-1-positive cells occur first along the atrioventricular sulcus of the diaphragmatic surface and then along the great arteries. Lumenized tubules appear, arranged in rows or in a lattice. They are more conspicuous in dorsal atrioventricular junction, along the major venous and coronary artery branches and at the base of the aorta and the pulmonary trunk extending toward the heart apex. At later stages, some segments of the lymphatic vessels are partially surrounded by smooth muscle cells. Possible mechanisms of lymphangiogenesis are: addition of Lyve-1-positive cells to the existing tubules, elongation of the lymphatic lattice, sprouting and coalescence of tubules. We discuss the existence of various subpopulations of endothelial cells among the Lyve-1-positive cells. Developmental Dynamics 237:2973-2986, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2008
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20. Communication between integrin receptors facilitates epicardial cell adhesion and matrix organization.
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Pae, So Hyun, Dokic, Danijela, and Dettman, Robert W.
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Formation of the epicardium requires interactions between α
4 β1 integrin, and the extracellular matrix. We investigated the role of other integrins expressed by epicardial cells. We detected transcripts for α5 , α8 , αv , β1 , β3 , and β5 integrins in the chick proepicardial organ (PE). We demonstrate that α5 β1 , α8 β1 , and αv β3 integrins are expressed by chick epicardial mesothelial cells (EMCs). Migration of EMCs in vitro was reduced by RGD-containing peptides. Using adenoviruses expressing an antisense to chick α4 ( AdGFPα 4AS), full-length ( Adhα 4V5), and C-terminal deleted α4 ( Adhα 4Δ CV5), we found that EMCs were less able to adhere to vitronectin and fibronectin120 indicating that α4 β1 plays a role in regulating EMC adhesion to ligands of α5 β1 , α8 β1 , and αv β3 . In Adhα 4Δ CV5-infected EMCs, α5 β1 was diminished in fibrillar adhesions and new FN matrix assembly was abnormal. We propose that cooperation between α4 β1 and RGD integrins is important for EMC adhesion and subepicardial matrix formation. Developmental Dynamics 237:962-978, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]- Published
- 2008
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21. Cardiac malformations and myocardial abnormalities in podoplanin knockout mouse embryos: Correlation with abnormal epicardial development.
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Mahtab, Edris A.F., Wijffels, Maurits C.E.F., Van Den Akker, Nynke M.S., Hahurij, Nathan D., Lie-Venema, Heleen, Wisse, Lambertus J., DeRuiter, Marco C., Uhrin, Pavel, Zaujec, Jan, Binder, Bernd R., Schalij, Martin J., Poelmann, Robert E., and Gittenberger-De Groot, Adriana C.
- Abstract
Epicardium and epicardium-derived cells have been shown to be necessary for myocardial differentiation. To elucidate the function of podoplanin in epicardial development and myocardial differentiation, we analyzed podoplanin knockout mouse embryos between embryonic day (E) 9.5 and E15.5 using immunohistochemical differentiation markers, morphometry, and three-dimensional reconstructions. Podoplanin null mice have an increased embryonic lethality, possibly of cardiac origin. Our study reveals impairment in the development of the proepicardial organ, epicardial adhesion, and spreading and migration of the epicardium-derived cells. Mutant embryos show a hypoplastic and perforated compact and septal myocardium, hypoplastic atrioventricular cushions resulting in atrioventricular valve abnormalities, as well as coronary artery abnormalities. The epicardial pathology is correlated with reduced epithelial-mesenchymal transformation caused by up-regulation of E-cadherin, normally down-regulated by podoplanin. Our results demonstrate a role for podoplanin in normal cardiac development based on epicardial-myocardial interaction. Abnormal epicardial differentiation and reduced epithelial-mesenchymal transformation result in deficient epicardium-derived cells leading to myocardial pathology and cardiac anomalies. Developmental Dynamics 237:847-857, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2008
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22. Primary and immortalized mouse epicardial cells undergo differentiation in response to TGFβ.
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Austin, Anita F., Compton, Leigh A., Love, Joseph D., Brown, Christopher B., and Barnett, Joey V.
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Cells derived from the epicardium are required for coronary vessel development. Transforming growth factor β (TGFβ) induces loss of epithelial character and smooth muscle differentiation in chick epicardial cells. Here, we show that epicardial explants from embryonic day (E) 11.5 mouse embryos incubated with TGFβ1 or TGFβ2 lose epithelial character and undergo smooth muscle differentiation. To further study TGFβ Signaling, we generated immortalized mouse epicardial cells. Cells from E10.5, 11.5, and 13.5 formed tightly packed epithelium and expressed the epicardial marker Wilm's tumor 1 (WT1). TGFβ induced the loss of zonula occludens-1 (ZO-1) and the appearance of SM22α and calponin consistent with smooth muscle differentiation. Inhibition of activin receptor-like kinase (ALK) 5 or p160 rho kinase activity prevented the effects of TGFβ while inhibition of p38 mitogen activated protein (MAP) kinase did not. These data demonstrate that TGFβ induces epicardial cell differentiation and that immortalized epicardial cells provide a suitable model for differentiation. Developmental Dynamics 237:366-376, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2008
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23. Serosal mesothelium retains vasculogenic potential.
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Kawaguchi, Michiya, Bader, David M., and Wilm, Bettina
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Mesothelia comprise the epithelial covering of coelomic organs and line the cavities in which they are housed. Mesothelia contribute to the vasculature of the heart and the intestinal tract by developmental processes of epithelial-mesenchymal transition (EMT), migration, and differentiation into endothelial cells, vascular smooth muscle cells, and pericytes. Here, we establish a novel in vitro system to analyze the differentiative potential of mesothelia. Using explants from serosal mesothelium (the mesothelial covering of the gut), we demonstrate that much of the developmental program observed in embryonic mesothelia is retained in the adult structure. Namely, processes of epithelial spreading, EMT, and differentiation into smooth muscle cells from these cells are observed. Interestingly, we were unable to stimulate endothelial cell differentiation using serum or various signaling factors. Taken together, these data reveal that differentiated serosal cells retain vasculogenic potential and provide a generalizable model for future studies on the developmental and differentiative capacity of the mesothelial cell type. Developmental Dynamics 236:2973-2979, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2007
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