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Sphingosine 1‐Phosphate receptor 1 (S1P1, encoded by S1pr1) is a G protein‐coupled receptor that signals in multiple cell types including endothelial cells and cardiomyocytes. Cardiomyocyte‐specific deletion of S1pr1 during mouse development leads to ventricular noncompaction, with 44% of mutant mice surviving to adulthood. Adult survivors of embryonic cardiomyocyte S1pr1 deletion showed cardiac hypertrabeculation consistent with ventricular noncompaction. Surprisingly, systolic function in mutant mice was preserved through at least 1 year of age. Cardiac conduction was abnormal in cardiomyocyte S1pr1 mutant mice, with prolonged QRS intervals in mutants as compared with littermate control mice. Immunostaining of hearts from S1pr1 mutant embryos displayed a zone of intermediate Connexin 40 (Cx40) expression in the trabecular myocardium. However, we observed no significant differences in Cx40 and Connexin 43 immunostaining in hearts from adult survivors of embryonic cardiomyocyte S1pr1 deletion, which suggests normalized development of the ventricular conduction system in mutant mice. By contrast, the adult survivors of embryonic cardiomyocyte S1pr1 deletion showed increased cardiac fibrosis as compared with littermate controls. These results demonstrate that ventricular hypertrabeculation caused by embryonic deletion of cardiomyocyte S1pr1 correlates with cardiac fibrosis, which contributes to abnormal ventricular conduction. These results also reveal conduction abnormalities in the setting of hypertrabeculation with normal systolic function, which may be of clinical relevance in humans with ventricular hypertrabeculation. [ABSTRACT FROM AUTHOR]

The initial intraembryonic vasculogenesis occurs in the cardiogenic mesoderm. Here, a cell population of proendocardial cells detaches from the mesoderm that subsequently generates the single endocardial tube by forming vascular plexuses. In the course of embryogenesis, the endocardium retains vasculogenic, angiogenic and haematopoietic potential. The coronary blood vessels that sustain the rapidly expanding myocardium develop in the course of the formation of the cardiac loop by vasculogenesis and angiogenesis from progenitor cells of the proepicardial serosa at the venous pole of the heart as well as from the endocardium and endothelial cells of the sinus venosus. Prospective coronary endothelial cells and progenitor cells of the coronary blood vessel walls (smooth muscle cells, perivascular cells) originate from different cell populations that are in close spatial as well as regulatory connection with each other. Vasculo‐ and angiogenesis of the coronary blood vessels are for a large part regulated by the epicardium and epicardium‐derived cells. Vasculogenic and angiogenic signalling pathways include the vascular endothelial growth factors, the angiopoietins and the fibroblast growth factors and their receptors. [ABSTRACT FROM AUTHOR]

The atrial septum enables efficient oxygen transport by separating the systemic and pulmonary venous blood returning to the heart. Only in placental mammals will the atrial septum form by the coming‐together of the septum primum and the septum secundum. In up to one of four placental mammals, this complex morphogenesis is incomplete and yields patent foramen ovale. The incidence of incomplete atrial septum is unknown for groups with the septum primum only, such as birds and reptiles. We found a low incidence of incomplete atrial septum in 11 species of bird (0% of specimens) and 13 species of reptiles (3% of specimens). In reptiles, there was a trabecular interface between the atrial septum and the atrial epicardium which was without a clear boundary between left and right atrial cavities. In developing reptiles (four squamates and one crocodylian), the septum primum initiated as a sheet that acquired perforations and the trabecular interface developed late. We conclude that atrial septation from the septum primum only results in a low incidence of incompleteness. In reptiles, the atrial septum and atrial wall develop a trabecular interface, but previous studies on atrial hemodynamics suggest this interface has a very limited capacity for shunting. Research Highlights: # We assessed the atrial septum in 11 species of birds and 13 species of reptiles. # Birds and reptiles appear to have a lower incidence of incomplete atrial septum than placental mammals [ABSTRACT FROM AUTHOR]

During embryonic development, organ morphogenesis requires major tissue rearrangements that are tightly regulated at the genetic level. A large number of studies performed in recent decades assigned a central role to programmed cell death for such morphogenetic tissue rearrangements that often sculpt the shape of embryonic organs. However, accumulating evidence indicates that far from being the only factor responsible for sculpting organ morphology, programmed cell death is accompanied by other tissue remodeling events that ensure the outcome of morphogenesis. In this regard, cell senescence has been recently associated with morphogenetic degenerative embryonic processes as an early tissue remodeling event in development of the limbs, kidney and inner ear. Here, we have explored cell senescence by monitoring β‐galactosidase activity during embryonic heart development where programmed cell death is believed to exert an important morphogenetic function. We report the occurrence of extensive cell senescence foci during heart morphogenesis. These foci overlap spatially and temporally with the areas of programmed cell death that are associated with remodeling of the outflow tract to build the roots of the great arteries and with the septation of cardiac cavities. qPCR analysis allowed us to identify a gene expression profile characteristic of the so‐called senescence secretory associated phenotype in the remodeling outflow tract of the embryonic heart. In addition, we confirmed local upregulation of numerous tumor suppressor genes including p21, p53, p63, p73 and Btg2. Interestingly, the areas of cell senescence were also accompanied by intense lysosomal activation and non‐apoptotic DNA damage revealed by γH2AX immunolabeling. Considering the importance of sustained DNA damage as a triggering factor for cell senescence and apoptosis, we propose the coordinated contribution of DNA damage, senescence and apoptotic cell death to assure tissue remodeling in the developing vertebrate heart. [ABSTRACT FROM AUTHOR]

Background: During heart development, it has been hypothesized that apoptosis of atrioventricular canal myocardium and replacement by fibrous tissue derived from the epicardium are imperative to develop a mature atrioventricular conduction. To test this, apoptosis was blocked using an established caspase inhibitor and epicardial growth was delayed using the experimental epicardial inhibition model, both in chick embryonic hearts. Results: Chicken embryonic hearts were either treated with the peptide caspase inhibitor zVAD‐fmk by intrapericardial injection in ovo (ED4) or underwent epicardial inhibition (ED2.5). Spontaneously beating embryonic hearts isolated (ED7–ED8) were then stained with voltage‐sensitive dye Di‐4‐ANEPPS and imaged at 0.5–1 kHz. Apoptotic cells were quantified (ED5–ED7) by whole‐mount LysoTracker Red and anti‐active caspase 3 staining. zVAD‐treated hearts showed a significantly increased proportion of immature (base to apex) activation patterns at ED8, including ventricular activation originating from the right atrioventricular junction, a pattern never observed in control hearts. zVAD‐treated hearts showed decreased numbers of apoptotic cells in the atrioventricular canal myocardium at ED7. Hearts with delayed epicardial outgrowth showed also increased immature activation patterns at ED7.5 and ED8.5. However, the ventricular activation always originated from the left atrioventricular junction. Histological examination showed no changes in apoptosis rates, but a diminished presence of atrioventricular sulcus tissue compared with controls. Conclusions: Apoptosis in the atrioventricular canal myocardium and controlled replacement of this myocardium by epicardially derived HCN4‐/Trop1‐ sulcus tissue are essential determinants of mature ventricular activation pattern. Disruption can lead to persistence of accessory atrioventricular connections, forming a morphological substrate for ventricular pre‐excitation. Developmental Dynamics 247:1033‐1042, 2018. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Background: Coexistence of idiopathic left fascicular ventricular tachycardia (ILFVT) and atrioventricular nodal reentrant tachycardia (AVNRT) has been rarely reported. Objectives: The study aimed at elucidating the prevalence of coexisted AVNRT in patients with ILFVT during longitudinal follow‐up. The electrophysiological properties and clinical predictors of coexisted ILFVT and AVNRT were investigated. Methods: From 1999 to 2017, a total of 108 patients (age: 33.7 ± 14.3, 84 male) with ILFVT from one tertiary center were consecutively enrolled. The prevalence of coexisted arrhythmias was explored during a longitudinal follow‐up and the electrophysiological parameters from the index procedure were compared. Results: During a mean follow‐up period of 106.8 ± 69.5 months, 21 of 108 patients (19.4%) had coexisted AVNRT. The electrophysiological study demonstrated patients with coexisted ILFVT and AVNRT were characterized by more antegrade dual AV node conduction (52.4% vs. 19.5%, P = 0.002; 9.5%), shorter antegrade slow pathway effective refractory period (285.1 ± 34.1 ms vs. 329.2 ± 69.2 ms, P = 0.034), longer retrograde fast pathway effective refractory period (368.9 ± 56.7 ms vs. 312.5 ± 95.2, P = 0.036), and less VA dissociation (19.0% vs. 60.9%, P = 0.001) than those without a coexisted AVNRT. Multivariate logistic analysis showed that presence of antegrade dual AV nodal physiology and retrograde VA conduction could predict a coexisted AVNRT in patients with ILFVT (P = 0.005, OR: 4.80, 95% CI: 1.65–14.37 and P = 0.002, OR: 0.14, 95% CI: 0.04–0.49, respectively). Conclusion: There was a high prevalence of coexisted AVNRT in patients with ILFVT during longitudinal follow‐up. The presence of antegrade dual AV nodal physiology and retrograde VA conduction can predict the coexisted AVNRT in patients with ILFVT. [ABSTRACT FROM AUTHOR]

Recent studies have shown that left ventricle (LV) exhibits considerable transmural differences in active mechanical properties induced by transmural differences in electrical activity, excitation-contraction coupling, and contractile properties of individual myocytes. It was shown that the time between electrical and mechanical activation of myocytes (electromechanical delay: EMD) decreases from subendocardium to subepicardium and, on the contrary, the myocyte shortening velocity (MSV) increases in the same direction. To investigate the physiological importance of this inhomogeneity, we developed a new finite element model of LV incorporating the observed transmural gradients in EMD and MSV. Comparative simulations with the model showed that when EMD or MSV or both were set constant across the LV wall, the LV contractility during isovolumic contraction (IVC) decreased significantly (dp/dtmax⁡  was reduced by 2 to 38% and IVC was prolonged by 18 to 73%). This was accompanied by an increase of transmural differences in wall stress. These results suggest that the transmural differences in EMD and MSV play an important role in physiological contractility of LV by synchronising the contraction of individual layers of ventricular wall during the systole. Reduction or enhancement of these differences may therefore impair the function of LV and contribute to heart failure. [ABSTRACT FROM AUTHOR]

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]

Heart development requires coordinated activity of various factors, the disturbance of which can lead to congenital heart defects. Heart lectin-associated matrix protein-1 ( hLAMP-1) is a matrix protein expressed within Hensen's node at Hamburger-Hamilton ( HH) stage 4, in the lateral mesoderm by HH stages 5-6 and enhanced within the left pre-cardiac field at HH stage 7. At HH stages 15-16, hLAMP-1 expression is observed in the atrioventricular canal and the outflow tract. Also, the role of hLAMP-1 in induction of mesenchyme formation in chick heart has been well documented. To further elucidate the role of this molecule in heart development, we examined its expression patterns during HH stages 8-14 in the chick. In this regard, we immunostained sections of the heart during HH stages 8-14 with antibodies specific to hLAMP-1. Our results showed prominent expression of hLAMP-1-positive particles in the extracellular matrix associated with the pre-cardiac mesoderm, the endoderm, ectoderm as well as neuroectoderm at HH stages 8-9. After formation of the linear heart tube at HH stage 10, the expression of hLAMP-1-stained particles disappears in those regions of original contact between the endoderm and heart forming fields due to rupture of the dorsal mesocardium while their expression becomes confined to the arterial and venous poles of the heart tube. This expression pattern is maintained until HH stage 14. This expression pattern suggests that hLAMP-1 may be involved in the formation of the endocardial tube. [ABSTRACT FROM AUTHOR]

The morpho-functional properties of the distal section of the cardiac Purkinje network (PN) and the Purkinje-myocardial junctions (PMJs) are fundamental to understanding the sequence of electrical activation in the heart. The overall structure of the system has already been described, and several computational models have been developed to gain insight into its involvement in cardiac arrhythmias or its interaction with implantable devices, such as pacemakers. However, anatomical descriptions of the PN in the literature have not enabled enough improvements in the accuracy of anatomical-based electrophysiological simulations of the PN in 3D hearts models. In this work, we study the global distribution and morphological properties of the PN, with special emphasis on the cellular and architectural characterization of its intramural branching structure, mesh-like sub-endocardial network, and the PMJs in adult pig hearts by both histopathological and morphometric evaluation. We have defined three main patterns of PMJ: contact through cell bodies, contact through cell prolongations either thick or piliform, and contact through transitional cells. Moreover, from hundreds of micrographs, we quantified the density of PMJs and provided data for the basal/medial/apical regions, anterior/posterior/septal/lateral regions and myocardial/sub-endocardial distribution. Morphometric variables, such as Purkinje cell density and thickness of the bundles, were also analyzed. After combining the results of these parameters, a different septoanterior distribution in the Purkinje cell density was observed towards the cardiac apex, which is associated with a progressive thinning of the conduction bundles and the posterolateral ascension of intramyocardial terminal scattered fibers. The study of the PMJs revealed a decreasing trend towards the base that may anatomically explain the early apical activation. The anterolateral region contains the greatest number of contacts, followed by the anterior and septal regions. This supports the hypothesis that thin distal Purkinje bundles create a junction-rich network that may be responsible for the quick apical depolarization. The PN then ascends laterally and spreads through the anterior and medial walls up to the base. We have established the first morphometric study of the Purkinje system, and provided quantitative and objective data that facilitate its incorporation into the development of models beyond gross and variable pathological descriptions, and which, after further studies, could be useful in the characterization of pathological processes or therapeutic procedures. [ABSTRACT FROM AUTHOR]

An editorial is presented on Atrioventricular (AV) discordance, is an uncommon form of congenital heart disease. The right atrium is connected to the morphological left ventricle through the mitral valve and the left atrium to the morphologically right ventricle through the tricuspid valve. Ventricle and mitral valve are located to the right and connected to the pulmonary artery.

Background: Multiple mechanisms have been proposed for idiopathic premature ventricular contractions (PVCs) originating from the outflow tracts (OTs). Recent observations such as the coexistence of these arrhythmias with atrioventricular nodal reentrant tachycardias and the association between discrete prepotentials and successful ablation sites of ventricular arrhythmias (VAs) from the OTs suggest a common link. Objective: In this case series we draw attention to a unique association between accessory pathways (APs) and idiopathic PVCs from the OTs, disappearing after AP ablation. Methods: We identified 6 cases in collaboration with several international electrophysiology centers, which presented with pre-excitation in association with OT, and in 1 case inflow tract (IT), PVCs on 12-lead surface ECG. Results: Six cases displayed pre-excitation and PVCs, in 5 cases originating from the right ventricular outflow tract (RVOT) and in 1 case from the right ventricular inflow tract (RVIT). In all patients, PVCs were monomorphic and had fixed coupling intervals, in 3 cases presenting in bigeminy. Catheter ablation of the AP led to the simultaneous disappearance of PVCs in 5 of 6 cases. The sites of ablation were remote from the OTs in all these cases. In most cases, the occurrence of OT PVCs was closely associated with the presence of pre-excitation. Conclusion: The coexistence of pre-excitation and PVCs from the OTs and the fact that in 5 of 6 cases PVCs disappeared after AP ablation suggests a common mechanism for arrhythmia genesis. [ABSTRACT FROM AUTHOR]

Hepatic malignancy with regional lymph node involvement is generally associated with poor prognosis. Lymphatic drainage from the liver to extrahepatic lymph nodes follows a complex and unpredictable pathway. To add to the complexity of management of regional lymph nodes in hepatic malignancies, not all liver cancers have the same propensity to metastasize through lymphatics. Lymphadenectomy has had mixed results in terms of improving patient survival. Other therapies especially anti-lymphogenic agents might play a role in the near future. [ABSTRACT FROM AUTHOR]

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]

Editorial. Discusses the development of the cardiac conduction system. Molecular analysis of cardiac morphogenesis; Expression of beta-galactosidase reporter gene in the developing or mature cardiac conduction systems; Patterns of contractile activity.

Migratory failure of somitic cells is the commonest explanation for ventral body wall defects. However, the embryo increases ~ 25-fold in volume in the period that the ventral body wall forms, so that differential growth may, instead, account for the observed changes in topography. Human embryos between 4 and 10 weeks of development were studied, using amira® reconstruction and cinema 4D® remodeling software for visualization. Initially, vertebrae and ribs had formed medially, and primordia of sternum and hypaxial flank muscle primordium laterally in the body wall at Carnegie Stage ( CS)15 (5.5 weeks). The next week, ribs and muscle primordium expanded in ventrolateral direction only. At CS18 (6.5 weeks), separate intercostal and abdominal wall muscles differentiated, and ribs, sterna, and muscles began to expand ventromedially and caudally, with the bilateral sternal bars fusing in the midline after CS20 (7 weeks) and the rectus muscles reaching the umbilicus at CS23 (8 weeks). The near-constant absolute distance between both rectus muscles and approximately fivefold decline of this distance relative to body circumference between 6 and 10 weeks identified dorsoventral growth in the dorsal body wall as determinant of the 'closure' of the ventral body wall. Concomitant with the straightening of the embryonic body axis after the 6th week, the abdominal muscles expanded ventrally and caudally to form the infraumbilical body wall. Our data, therefore, show that the ventral body wall is formed by differential dorsoventral growth in the dorsal part of the body. [ABSTRACT FROM AUTHOR]

Ebstein's anomaly is a complex congenital lesion which primarily involves the tricuspid valve. The tricuspid leaflets are tethered to varying degrees to the right ventricular free wall and the ventricular septum often resulting in significant tricuspid regurgitation and a small functioning right ventricular chamber. Although the septal leaflet originates normally at the right atrioventricular junction, the proximal portion is often completely tethered to the ventricular septum resulting in a misconception and erroneous statements in many publications that its attachment is apically displaced. Although two-dimensional echocardiography represents the primary modality for the diagnosis of this anomaly, three-dimensional echocardiography provides incremental value in characterizing the extent and severity of tethering of individual tricuspid valve leaflets. This information is useful in surgical decision making whether to repair or replace the tricuspid valve. [ABSTRACT FROM AUTHOR]

Background: Growth promoting signals from the epicardium are essential for driving myocardial proliferation during embryogenesis. In adults, these signals become reactivated following injury and promote angiogenesis and myocardial repair. Therefore, identification of such paracrine factors could lead to novel therapeutic strategies. The multi-functional peptide adrenomedullin ( Adm = gene, AM = protein) is required for normal heart development. Moreover, elevated plasma AM following myocardial infarction offers beneficial cardioprotection and serves as a powerful diagnostic and prognostic indication of disease severity. Results: Here, we developed a new model of Adm overexpression by stabilizing the Adm mRNA through gene-targeted replacement of the endogenous 3′ untranslated region. As expected, Admhi/hi mice express three-times more AM than controls in multiple tissues, including the heart. Despite normal blood pressures, Admhi/hi mice unexpectedly showed significantly enlarged hearts due to increased cardiac hyperplasia during development. The targeting vector was designed to allow for reversion to wild-type levels by means of Cre-mediated modification. Using this approach, we demonstrate that AM derived from the epicardium, but not the myocardium or cardiac fibroblast, is responsible for driving cardiomyocyte hyperplasia. Conclusions: AM is produced by the epicardium and drives myocyte proliferation during development, thus representing a novel and clinically relevant factor potentially related to mechanisms of cardiac repair after injury. Developmental Dynamics 243:243-256, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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]

Background: The ventricular conduction system (VCS) coordinates the heartbeat and is composed of central components (the atrioventricular node, bundle, and right and left bundle branches) and a peripheral Purkinje fiber network. Conductive myocytes develop from common progenitor cells with working myocytes in a bimodal process of lineage restriction followed by limited outgrowth. The lineage relationship between progenitor cells giving rise to different components of the VCS is unclear. Results: Cell lineage contributions to different components of the VCS were analysed by a combination of retrospective clonal analysis, regionalized transgene expression studies, and genetic tracing experiments using Connexin40-GFP mice that precisely delineate the VCS. Analysis of a library of hearts containing rare large clusters of clonally related myocytes identifies two VCS lineages encompassing either the right Purkinje fiber network or left bundle branch. Both lineages contribute to the atrioventricular bundle and right bundle branch that segregate early from working myocytes. Right and left VCS lineages share the transcriptional program of the respective ventricular working myocytes and genetic tracing experiments discount alternate progenitor cell contributions to the VCS. Conclusions: The mammalian VCS is comprised of cells derived from two lineages, supporting a dual contribution of first and second heart field progenitor cells. Developmental Dynamics 242:665-677, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Perturbations in cardiac development result in congenital heart disease, the leading cause of birth defect-related infant morbidity and mortality. Advances in cardiac developmental biology have significantly augmented our understanding of signalling pathways and transcriptional networks underlying heart formation. Cardiogenesis is initiated with the formation of mesodermal multipotent cardiac progenitor cells and is governed by cross-talk between developmental cues emanating from endodermal, mesodermal and ectodermal cells. The molecular and transcriptional machineries that direct the specification and differentiation of these cardiac precursors are part of an evolutionarily conserved programme that includes the Nkx-, Gata-, Hand-, T-box- and Mef2 family of transcription factors. Unravelling the hierarchical networks governing the fate and differentiation of cardiac precursors is crucial for our understanding of congenital heart disease and future stem cell-based and gene therapies. Recent molecular and genetic lineage analyses have revealed that subpopulations of cardiac progenitor cells follow distinctive specification and differentiation paths, which determine their final contribution to the heart. In the last decade, progenitor cells that contribute to the arterial pole and right ventricle have received much attention, as abnormal development of these cells frequently results in congenital defects of the aortic and pulmonary outlets, representing the most commonly occurring congenital cardiac defects. In this review, we provide an overview of the building plan of the vertebrate four-chambered heart, with a special focus on cardiac progenitor cell specification, differentiation and deployment during arterial pole development. [ABSTRACT FROM AUTHOR]

Mesothelium is the simple squamous epithelium covering all abdominal organs and the coeloms in which those organs reside. While the structural characteristics of this cell type were documented a century ago, its potential in development, disease, and wound healing is only now becoming apparent. In the embryo, mesothelia provide vasculogenic cells for the developing heart, lungs, and gut. Furthermore, adult mesothelial cells can be reactivated using thymosin β4 and mobilized to aid in tissue repair. Despite their positive role in development and repair, mesothelia are also susceptible to adhesion and tumor formation. With knowledge that the mesothelium is an important mediator of tissue repair as well as disease, it will be important to identify other factors like thymosin β4 that have the ability to potentiate these cells. Future use of chemical and genetic agents in conjunction with mesothelial cells will lead to enhanced therapeutic potential and mitigation of deleterious outcomes. [ABSTRACT FROM AUTHOR]

Background: Understanding of cardiac outflow tract (OFT) remodeling is essential to explain repositioning of the aorta and pulmonary orifice. In wild type embryos (E9.5-14.5), second heart field contribution (SHF) to the OFT was studied using expression patterns of Islet 1, Nkx2.5, MLC-2a, WT-1, and 3D-reconstructions. Abnormal remodeling was studied in VEGF120/120 embryos. Results: In wild type, Islet 1 and Nkx2.5 positive myocardial precursors formed an asymmetric elongated column almost exclusively at the pulmonary side of the OFT up to the pulmonary orifice. In VEGF120/120 embryos, the Nkx2.5-positive mesenchymal population was disorganized with a short extension along the pulmonary OFT. Conclusions: We postulate that normally the pulmonary trunk and orifice are pushed in a higher and more frontal position relative to the aortic orifice by asymmetric addition of SHF-myocardium. Deficient or disorganized right ventricular OFT expansion might explain cardiac malformations with abnormal position of the great arteries, such as double outlet right ventricle. Developmental Dynamics 241:1413-1422, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Introduction: Muscles can adapt their fiber properties to accommodate to new conditions. We investigated the extent to which a decrease in muscle activation can cause an adaptation of fiber properties in synergistic and antagonistic jaw muscles. Methods: Three months after the injection of botulinum toxin type A in one masseter (anterior or posterior) muscle changes in fiber type composition and fiber cross-sectional areas in jaw muscles were studied at the microscopic level. Results: The injected masseter showed a steep increase in myosin type IIX fibers, whereas fast fibers decreased by about 50% in size. Depending on the injection site, both synergistic and antagonistic muscles showed a significant increase in the size of their fast IIA fibers, sometimes combined with an increased number of IIX fibers. Conclusion: Silencing the activity in the masseter not only causes changes in the fibers of the injected muscle but also leads to changes in other jaw muscles. Muscle Nerve, 2012 [ABSTRACT FROM AUTHOR]

Mucociliary clearance is essential to maintain the defense function of the maxillary sinus; however, no literatures described the age changes in its lining epithelium. Therefore, the current work sought to describe the morphological postnatal age-related changes of maxillary sinus lining epithelium in rats using light, transmission, and scanning electron microscopes. Eighteen albino rats were divided into six groups according to their ages: 2-week-old, 1-month-old, 2-month-old, 3-month-old, adults, and senile rats. One-month-old-rats' group was the first to have recognizable maxillary sinus cavities that were lined by either single flat cellular layer or two distinct epithelial layers. These cells were devoid of microvilli and cilia, none of them showed evidence of differentiation into identifiable cell types. In 2- and 3-month-old rats, the mucosa of maxillary sinus started to be lined with pseudostratified epithelium with apparent increase in both microvilli and cilia. The first indication of goblet cell differentiation was observed in 3-month-old-rats. In the adult rats, the sinuses became completely lined by mature respiratory epithelium. However, in senile rats the epithelium exhibited polyps with clumped cilia and some areas of stratification and desquamation. Goblet cells were scanty and degenerating. The impaired mucociliary components (epithelium, cilia, and goblet cells' mucus) found in young and old ages of the current work might be correlated to human to explain predisposition of rhino-sinusitis in these age groups. Microsc. Res. Tech., 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

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]

The heart of lung-breathing vertebrates normally shows an asymmetric arrangement of its venoatrial connections along the left-right (L-R) body axis. The systemic venous tributaries empty into the right atrium while the pulmonary venous tributaries empty into the left atrium. The ways by which this asymmetry evolves from the originally symmetrically arranged embryonic venous heart pole are poorly defined. Here we document the development of the venous heart pole in Xenopus laevis (stages 40-46). We show that, prior to the appearance of the mouth of the common pulmonary vein (MCPV), the systemic venous tributaries empty into a bilaterally symmetric chamber (sinus venosus) that is demarcated from the developing atriums by a circular ridge of tissue (sinu-atrial ridge). A solitary MCPV appears during stage 41. From the time point of its first appearance onwards, the MCPV lies cranial to the sinu-atrial ridge and to the left of the developing interatrial septum and body midline. L-R lineage analysis shows that the interatrial septum and MCPV both derive from the left body half. The CPV, therefore, opens from the beginning into the future left atrium. The definitive venoatrial connections are established by the formation of a septal complex that divides the lumen of the venous heart pole into systemic and pulmonary venous flow pathways. This complex arises from the anlage of the interatrial septum and the left half of the sinu-atrial ridge. Developmental Dynamics 240:1518-1527, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]