Document Detail

Concepts of cardiac development in retrospect.
Jump to Full Text
MedLine Citation:
PMID:  19184179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent research, enabled by powerful molecular techniques, has revolutionized our concepts of cardiac development. It was firmly established that the early heart tube gives rise to the left ventricle only, and that the remainder of the myocardium is recruited from surrounding mesoderm during subsequent development. Also, the cardiac chambers were shown not to be derived from the entire looping heart tube, but only from the myocardium at its outer curvatures. Intriguingly, many years ago, classic experimental embryological studies reached very similar conclusions. However, with the current scientific emphasis on molecular mechanisms, old morphological insights became underexposed. Since cardiac development occurs in an architecturally complex and dynamic fashion, molecular insights can only fully be exploited when placed in a proper morphological context. In this communication we present excerpts of important embryological studies of the pioneers of experimental cardiac embryology of the previous century, to relate insights from the past to current observations.
Authors:
Gert van den Berg; Antoon F M Moorman
Related Documents :
24844719 - Toronto heart attack collaborative: an administrative model that facilitated a successf...
25234389 - Atrial fibrillation: antiarrhythmic therapy.
25331159 - Hold or fold - proteins in advanced heart failure and myocardial recovery.
22103459 - Rare case of isolated levocardia with polysplenia including normally structured lung wi...
25328889 - Normoxic and hyperoxic cardiopulmonary bypass in congenital heart disease.
25488019 - The spatial distribution of actin and mechanical cycle of myosin are different in right...
15075429 - Precipitating factors for systolic and diastolic heart failure: a four-year follow-up o...
15851339 - Comparison of stimulation sites within left ventricular veins on the acute hemodynamic ...
1503329 - Return to work after uncomplicated myocardial infarction: a trial of practice guideline...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-30
Journal Detail:
Title:  Pediatric cardiology     Volume:  30     ISSN:  1432-1971     ISO Abbreviation:  Pediatr Cardiol     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-08     Completed Date:  2009-08-18     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  8003849     Medline TA:  Pediatr Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  580-7     Citation Subset:  IM    
Affiliation:
Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Fetal Heart / embryology*
Heart / embryology
Heart Ventricles / embryology
Humans
Mesoderm / embryology
Veins / embryology
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Pediatr Cardiol
ISSN: 0172-0643
ISSN: 1432-1971
Publisher: Springer-Verlag, New York
Article Information
Download PDF
© The Author(s) 2009
Received Day: 9 Month: 12 Year: 2008
Accepted Day: 22 Month: 12 Year: 2008
Electronic publication date: Day: 30 Month: 1 Year: 2009
Print publication date: Month: 7 Year: 2009
Volume: 30 Issue: 5
First Page: 580 Last Page: 587
ID: 2691808
PubMed Id: 19184179
Publisher Id: 9369
DOI: 10.1007/s00246-008-9369-y
issue-copyright-statement: © Springer Science+Business Media, LLC 2009

Concepts of Cardiac Development in Retrospect
Gert van den Berg1
Antoon F. M. Moorman12 Address: A.F.Moorman@amc.uva.nl
1Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands
2Department of Anatomy & Embryology, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands

Introduction

The introduction of molecular techniques to developmental biology has greatly empowered research on cardiac development and has led to some important shifts of paradigm. For instance, it is now firmly established that the initially formed heart tube does not contain all prospective cardiac chambers, but that it is mainly fated to become the left ventricle, while the remainder of the myocardium is added during subsequent development (Fig. 1) [3]. Furthermore, the cardiac chambers were shown not to originate from circumferential segments around the early straight tubular heart, but to balloon out from the outer curvatures of the looping heart tube [22]. Remarkably, traditional morphological embryology, relying on limited experimental techniques, reached very similar conclusions, as we show in a few examples.

With the advent of molecular biology as a powerful and productive discipline in embryology, scientific emphasis became largely focused on cellular and molecular mechanisms that control the formation of the heart, while the morphological context of these processes became of lesser importance. Because the developing heart and its precursors rapidly transform in a spatially complex fashion, molecular data can only be interpreted in a proper three-dimensional (3D) context. It is, therefore, disappointing that morphological insights of heart formation are hardly incorporated into current-day molecular research on cardiac development. The complexity of interpreting morphological data using traditional 2D approaches may be an underlying cause. Fortunately, novel 3D reconstructions and other visualization techniques can fill this gap [31].

It is the goal of this article to place the new concepts of cardiac development in the context of classic morphological and physiological insights. We discuss excerpts of the meticulous work of pioneering researchers of cardiac development (namely, Bradley Patten, Robert DeHaan, and Victoria de la Cruz) to investigate whether their views harmonize with recent insights and to explore whether pre-existing morphological insights can stimulate the formulation of new hypotheses.


Fusion of the Vitelline Veins Forms the Early Heart

The current view on cardiac development is that the heart is formed by cells that originate from several embryonic fields [2]. Prior to this notion, however, only a single heart-forming region (HFR) was described [29, 30]. The classic consensus of the formation of the early heart tube from this HFR is depicted in Fig. 2. With gastrulation, intra-embryonic mesoderm is formed, which is then separated into a splanchnic and a somatic layer by formation of the coelomic cavity. The somatic mesoderm lines the ectoderm, and the splanchnic mesoderm lines the endoderm. Transplantation studies showed that the embryonic disc contains a left and a right heart-forming region HFR in its splanchnic mesoderm [29, 30]. Expression of important cardiac transcription factors such as Nxk2.5 [21], Gata4 [17], and e/dHand [40] underlines the cardiogenic capacity of this mesoderm.

The transformation of the HFR into a heart tube is morphologically complex. As illustrated by the transverse sections in Fig. 2, the lateral limits of the HFR luminize [9] and make endothelial cells [6]. This forming lumen is caudally contiguous with the vitelline veins, which cover the yolk sac. Cranially, the walls of these primitive vitelline veins will start to express sarcomeric proteins [9, 44] and will fuse in the embryonic midline to form the embryonic heart tube [7, 15, 26, 46, 47]. Shortly after fusion, the ventral side of the heart tube starts to twitch [32], which is followed shortly by rhythmic peristaltic contractions originating from the venous pole of the heart tube [20, 26].

The fact that cardiac and vessel precursors reside in neighboring developmental territories was also found to be of importance for the molecular control of their development. Knockdown of scl or etsrp, transcription factors that promote vessel formation, enlarged the heart field and increased the number of cardiomyocytes of zebrafish embryos. Conversely, overexpression of these “vessel-genes” reduced the heart field and the number of cardiomyocytes [35].


Transformation of the Heart-Forming Region with Folding

A new and important concept in heart development are the proposed multiple heart-forming fields. Cardiac precursors were shown to be added to both poles of the initially formed heart tube [3]. These precursors are thought to take origin from a second heart-forming field, primarily located in the coelomic wall that overlies the foregut [2]. In the previous century a large body of research was invested into the delineation of cardiac precursors within the embryonic disc, and into the transformation of these cells into the heart tube [29, 30, 42]. These studies, however, did not lead to the proposition of multiple heart-forming fields.

As previously pointed out, an explanation for not describing a second source of cardiac precursors might lie in the inability to culture embryos up to stages when addition of cells to the heart was completed [25]. This experimental disadvantage has most likely hampered the observation of the full extent of the original HFR. Nevertheless, addition at both poles of the heart tube does occur during the time frame of culturing. De la Cruz et al. excised the early heart tube of an embryo in culture. With culturing the pericardial cavity filled at both the venous and the arterial pole with newly forming myocardium [11]. This indicates that addition from what is currently called the second heart field could have been observed. Why it was not denoted as such may lie in the intricacy of the morphological transformations of the HFR during embryonic folding.

Folding can be regarded as the process by which both the cranial and the lateral aspects of the embryonic disc bend inward (Fig. 2) [42]. By this process the foregut is formed as a pocket in the endoderm and the left and right HFRs swing toward midline, thus forming the heart tube (Fig. 2). Inspection of the morphogenetic transformation of the HFR (sections in Fig. 2) shows that the lateral parts of the HFR fuse and luminize to form the ventral aspect of the heart tube. The medial parts of the heart fields, however, remain to contact the endoderm and will become the pericardial back wall. It is this back wall that is now said to contain the second heart field. The contact between the medial and the lateral mesoderm can later be recognized as the dorsal mesocardium. After rupture of this mesocardium, the medial mesoderm contacts the heart tube only at its venous and arterial poles.

These morphological details indicate that the original HFR is not the equivalent to the first heart field, and contains (at least a part of) the recently described second heart field. In line with this notion, previous radiolabeling of one side of the “classic” HFR showed unilateral marking of the endocardium, the myocardium, and the pericardial back wall [41]. Moreover, migration studies by Rosenquist and DeHaan already clearly showed that the original HFR contributes to both poles of the heart [30].


Developmental Plasticity of the Heart-Forming Region

A reason for classical embryologists not to segregate the HFR into more fields might be that they adhered to a stricter definition of an embryonic field. Such a field was defined to be an “area of tissue within which a certain process, such as [induction of an organ] occurs” [37]. In other words, cells within a limb field are committed to form a limb; cells within an eye field, to form an eye; and cells within a heart field, to form a heart. Therefore, if one would propose multiple fields within the HFR, this, by definition, would imply each proposed field to be committed to a specific fate. This, however, did not appear to be the case.

De Haan and coworkers transplanted tissue within the classic HFRs. In normal development, caudal tissue from the HFR forms myocardium that expresses an atrium-specific myosin and has a relatively high beat rate, while cranial tissue will form ventricular myosin-expressing myocardium with a lower beat rate. Interestingly, relocated cells adapted to the phenotype of their new surroundings: cranial tissue increased in beat rate when grafted caudally, while caudal tissue gave rise to ventricular myosin-expressing myocardium after being placed cranially [33, 34]. From these experiments DeHaan and coworkers concluded that “although pre-cardiac mesoderm is spatially organized to form particular cardiac tissues … the cells are not irreversibly committed … to a pre-determined pattern of physiological differentiation” [8]. This argues against a subdivision of the original HFRs into distinct fields.

The current separation of the HFR into multiple fields has, however, proven to be useful. It has led to knowledge of the molecular control of the formation of cardiomyocytes from precursors, which might be translated to regeneration-based therapeutics for heart disease. The underlying morphological mechanism of these observations might possibly be better explained otherwise. Classic studies support a model of a gradual formation of the heart from a single HFR, which, with embryonic folding, is molded in such a way that it can only add cells to the heart via its inflow and its outflow. The concept of just a single heart field is also supported by recent observations showing that marker genes of the second heart field are already expressed in the first heart field [1, 27, 48]. Our own lineage and proliferation studies also indicate a gradual formation of the heart tube from a single focus of rapidly proliferating cells in the splanchnic mesoderm [45].


The Fate of a Gradually Lengthening Heart Tube

As a consequence of the ongoing recruitment to the heart, the initially formed heart tube does not contain all prospective cardiac components. Recent data have shown that this early tube only gives rise to the future left ventricle [3]. An important parameter for understanding the growth of the heart tube is the regionalization of proliferation. In other words, is the inherent proliferation rate of early myocardium sufficient to account for the growth of the heart?

Previous publications with respect to this subject are scarce and contradicting, stating slow [36] as well as rapid [43] proliferation of the early heart tube. However, novel developed techniques [39] have enabled us to show that newly forming myocardium of embryos of both chicken [38, 45] and mouse (unpublished results) embryos does not proliferate. These studies further emphasize that early cardiac growth can only be achieved by recruitment of cardiomyocytes. This, and the notion of the left ventricular fate of the early heart, can also be deduced from classic observations, as we show below.

Figure 3 summarizes several experiments by De la Cruz et al. [1214]. The early heart was labeled at both its arterial (●) and its venous edges (▲), i.e., at the pericardial reflections. The initially placed cranial label could be observed to move caudal. This movement was recently also observed in the developing mouse heart [49]. Further tracing such an early cranial label (●) showed its presence in the ventricular septum. This observation was confirmed by recent cell tracings at our lab [28]. A label placed in the outflow tract at a later stage (○) ended up in the right ventricular free wall, showing that the right ventricle is formed by cardiomyocytes that are added to the heart at the arterial pole. At the venous pole, an early label could be traced to the left ventricular free wall of the four-chambered heart, while the later label (∆) was found in the left atrium, upstream of the mitral valve. So these tracing experiments not only show addition of myocardium at both poles of the heart tube, but also demonstrate that the initial tube is fated to become the left ventricle.

Because the heart tube is gradually formed by a caudal progression of the fusion of the left and right HFRs (Fig. 2), the fate of a caudally placed label will depend on the time of placement. The initial point of fusion, however, will form the ventricular septum, as indicated by the earliest cranial label (●). Recent genetic lineage analysis in mouse, performed in our lab, reached a similar conclusion (Aanhaanen, Christoffels, and coworkers; in preparation].


Chamber Formation: The Ballooning Model

In the previous paragraphs we discussed that not all cardiac chambers are present in the myocardium of the early heart tube. Further complicating the concept of heart development is that not all myocardium of the growing heart tube will form chambers. Although often schematically represented, the chambers do not differentiate as circumferential segments along the length of the heart tube but, rather, as modules perpendicular to the axis of the looping heart tube. This mechanism of heart development was dubbed the ballooning model [22]. Although conceptually more complex than most schematics, the ballooning model offers an excellent example of how a morphological model can lead to the unraveling of molecular mechanisms underlying heart formation.

Apart from displaying slow proliferation, newly formed myocardium is also poorly differentiated. It has underdeveloped sarcomeres and is weakly electrically coupled, leading to a sluggishly contracting tube. The phenotype of this myocardium resembles the nodes of the adult conduction system [22]. During development, a subset of the heart tube further differentiates into the working myocardium of the chambers. This process initiates specifically at the outer curvature of the looping heart tube [4, 23]. Why this process initiates at this location might be explained by the local intimate association of the endocardium and myocardium.

As illustrated in the sections in Fig. 2, the fusion of the primitive vitelline veins occurs in the ventral midline of the embryo. With this fusion, the endothelial layers also adjoin ventrally, where they contact the forming myocardium. In the heart, the endothelial cell layer is called the endocardium. With looping of the heart tube, the contact between endocardium and myocardium becomes located at the outer curvature. It has recently become clear that Notch signaling from the endocardium causes the myocardium to trabeculate [16], a hallmark of ventricular differentiation and occurring only at the outer curvature. Notch signaling depends on cell-cell contact, thus limiting this mechanism to the outer curvature.

Recent work from our lab showed that, prior to trabecularization, myocytes of the outer curvature of the looped heart enlarge in volume and then reinitiate proliferation [38]. This observation may suggest that cell-size-controlled pathways are important for myocyte proliferation and concomitant differentiation. At the proliferating outer curvatures, the myocardium also shows a local increase in conduction velocity [10], coinciding with the initiation of expression of gap-junctional proteins, such as Cx40 (Fig. 4). Also, the contractile apparatus of the chambers further develops at the outer curvatures [23]. Myocardium of the inner curvature, the atrioventricular canal, and the outflow tract remains poorly differentiated, resembling nodal myocardium.

The inner/outer curvature differentiation of the heart tube is tightly regulated by T-box transcription factors [24]. Tbx2 and Tbx3 were found to be specifically expressed in the above-described underdeveloped regions of the heart tube. Overexpression of Tbx2 in mice resulted in a failure of chamber differentiation [5]. Tbx3 is closely related to Tbx2 and is expressed in the developing conduction system of the heart [18]. Ectopic expression of this transcriptional repressor in working myocardium of the atria provoked an up-regulation of sinus node specific genes. Moreover, electrophysiological analysis of these atria showed the presence of ectopic nodal tissue [19].

The ballooning model is based on the recognition that cardiomyocytes of the initially formed heart tube resemble the nodes of the adult conduction system. The notion that, after looping of the heart tube, this phenotype is retained at the inner curvatures was supported by the observation that transcriptional repressors were expressed at the inner curvatures. These observations, and further functional analyses, provided insights into the formation of the sinus node which may offer clinical inroads regarding the development of bio-artificial pacemakers [19].


Conclusion

The ballooning model shows that the integration of morphological and physiological insights with recent molecular findings can lead to the unraveling of developmental mechanisms. Unfortunately, these old insights seldom are combined with current research on cardiac formation from precursors. The view that classic embryologists had of the developing heart is strikingly similar to the currently proposed models. This is nicely illustrated by a quote from an article by Bradley Patten in 1933: “The tubular heart is not formed all at once …. We must clearly recognize the fact that the part of the heart which we know in comparative anatomy as the sinus venosus is not established until after the ventricle and the atrium have been formed” [26].

Although lacking the power of molecular techniques, classic experiments have resulted in solid insights into the development of the heart, which are still proving to be valid. It is therefore worthwhile to incorporate molecular observations in a morphological framework, rather than using such observations for the postulation of new models of heart formation.


Notes

Presented at the Riley Heart Center Symposium on Cardiac Development, Indianapolis, 2008.

The authors are funded by the Netherlands Heart Foundation (NHS1996M002). They wish to thank Prof. Robert L. DeHaan, Dr. Jan M. Ruijter, Dr. Maurice J. B. van den Hoff, and Bram van Wijk, M.Sc., for valuable discussions and suggestions.

Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.


References
1.. Brade T,Gessert S,Kuhl M,Pandur P. The amphibian second heart field: Xenopus islet-1 is required for cardiovascular developmentDev Biol 2007;311:297–310. [doi: 10.1016/j.ydbio.2007.08.004]
1.. Brade T, Gessert S, Kuhl M, Pandur P (2007) The amphibian second heart field: Xenopus islet-1 is required for cardiovascular development. Dev Biol 311:297–310 [pmid: 17900553]
2.. Buckingham M,Meilhac S,Zaffran S. Building the mammalian heart from two sources of myocardial cellsNat Rev Genet 2005;6:826–837. [doi: 10.1038/nrg1710]
2.. Buckingham M, Meilhac S, Zaffran S (2005) Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet 6:826–837 [pmid: 16304598]
3.. Cai CL,Liang X,Shi Y,Chu PH,Pfaff SL,Chen J,Evans S. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heartDev Cell 2003;5:877–889. [doi: 10.1016/S1534-5807(03)00363-0]
3.. Cai CL, Liang X, Shi Y, Chu PH, Pfaff SL, Chen J, Evans S (2003) Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell 5:877–889 [pmid: 14667410]
4.. Christoffels VM,Habets PEMH,Franco D,Campione M,Jong F,Lamers WH,Bao ZZ,Palmer S,Biben C,Harvey RP,Moorman AFM. Chamber formation and morphogenesis in the developing mammalian heartDev Biol 2000;223:266–278. [doi: 10.1006/dbio.2000.9753]
4.. Christoffels VM, Habets PEMH, Franco D, Campione M, de Jong F, Lamers WH, Bao ZZ, Palmer S, Biben C, Harvey RP, Moorman AFM (2000) Chamber formation and morphogenesis in the developing mammalian heart. Dev Biol 223:266–278 [pmid: 10882515]
5.. Christoffels VM,Hoogaars WMH,Tessari A,Clout DEW,Moorman AFM,Campione M. T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambersDev Dyn 2004;229:763–770. [doi: 10.1002/dvdy.10487]
5.. Christoffels VM, Hoogaars WMH, Tessari A, Clout DEW, Moorman AFM, Campione M (2004) T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers. Dev Dyn 229:763–770 [pmid: 15042700]
6.. Coffin JD,Poole TJ. Embryonic vascular development: immunohistochemical identification of the origin and subsequent morphogenesis of the major vessel primordia in quail embryosDevelopment 1988;102:735–748.
6.. Coffin JD, Poole TJ (1988) Embryonic vascular development: immunohistochemical identification of the origin and subsequent morphogenesis of the major vessel primordia in quail embryos. Development 102:735–748 [pmid: 3048971]
7.. Davis CL. Development of the human heart from its first appearance to the stage found in embryos of twenty paired somitesContrib Embryol 1927;19:245–284.
7.. Davis CL (1927) Development of the human heart from its first appearance to the stage found in embryos of twenty paired somites. Contrib Embryol 19:245–284
8.. Haan RL,Fujii S,Satin J. Cell interactions in cardiac developmentDev Growth Differ 1990;32:233–241. [doi: 10.1111/j.1440-169X.1990.00233.x]
8.. de Haan RL, Fujii S, Satin J (1990) Cell interactions in cardiac development. Dev Growth Differ 32:233–241
9.. Jong F,Geerts WJC,Lamers WH,Los JA,Moorman AFM. Isomyosin expression pattern during formation of the tubular chicken heart: a three-dimensional immunohistochemical analysisAnat Rec 1990;226:213–227. [doi: 10.1002/ar.1092260211]
9.. de Jong F, Geerts WJC, Lamers WH, Los JA, Moorman AFM (1990) Isomyosin expression pattern during formation of the tubular chicken heart: a three-dimensional immunohistochemical analysis. Anat Rec 226:213–227 [pmid: 2137308]
10.. Jong F,Opthof T,Wilde AAM,Janse MJ,Charles R,Lamers WH,Moorman AFM. Persisting zones of slow impulse conduction in developing chicken heartsCirc Res 1992;71:240–250.
10.. de Jong F, Opthof T, Wilde AAM, Janse MJ, Charles R, Lamers WH, Moorman AFM (1992) Persisting zones of slow impulse conduction in developing chicken hearts. Circ Res 71:240–250 [pmid: 1628384]
11.. la Cruz MV,Sanchez-Gomez C. la Cruz M,Markwald RRStraight tube heart. Primitive cardiac cavities vs. primitive cardiac segmentsLiving morphogenesis of the heart 1998Boston: Birkhäuser; :85–98.
11.. De la Cruz MV, Sanchez-Gomez C (1998) Straight tube heart. Primitive cardiac cavities vs. primitive cardiac segments. In: De la Cruz M, Markwald RR (eds) Living morphogenesis of the heart. Birkhäuser, Boston, pp 85–98
12.. Cruz MV,Sanchez Gomez C,Arteaga MM,Arguëllo C. Experimental study of the development of the truncus and the conus in the chick embryoJ Anat 1977;123:661–686.
12.. De la Cruz MV, Sanchez Gomez C, Arteaga MM, Arguëllo C (1977) Experimental study of the development of the truncus and the conus in the chick embryo. J Anat 123:661–686 [pmid: 885781]
13.. Cruz MV,Sánchez-Gómez C,Palomino M. The primitive cardiac regions in the straight tube heart (stage 9) and their anatomical expression in the mature heart: an experimental study in the chick embryoJ Anat 1989;165:121–131.
13.. De la Cruz MV, Sánchez-Gómez C, Palomino M (1989) The primitive cardiac regions in the straight tube heart (stage 9) and their anatomical expression in the mature heart: an experimental study in the chick embryo. J Anat 165:121–131 [pmid: 17103606]
14.. Cruz MV,Sánchez-Gómez C,Cayré R. The developmental components of the ventricles their significance in congenital cardiac malformationsCard Young 1991;1:123–128.
14.. De la Cruz MV, Sánchez-Gómez C, Cayré R (1991) The developmental components of the ventricles their significance in congenital cardiac malformations. Card Young 1:123–128
15.. deRuiter MC,Poelmann RE,VanderPlas-de Vries I,Mentink MM,Gittenberger-de Groot AC. The development of the myocardium and endocardium in mouse embryos. Fusion of two heart tubes?Anat Embryol (Berl) 1992;185:461–473.
15.. deRuiter MC, Poelmann RE, VanderPlas-de Vries I, Mentink MM, Gittenberger-de Groot AC (1992) The development of the myocardium and endocardium in mouse embryos. Fusion of two heart tubes? Anat Embryol (Berl) 185:461–473 [pmid: 1567022]
16.. Grego-Bessa J,Luna-Zurita L,del Monte G,Bolos V,Melgar P,Arandilla A,Garratt AN,Zang H,Mukouyama YS,Chen H,Shou W,Ballestar E,Esteller M,Rojas A,Perez-Pomares JM,la Pompa JL. Notch signaling is essential for ventricular chamber developmentDev Cell 2007;12:415–429. [doi: 10.1016/j.devcel.2006.12.011]
16.. Grego-Bessa J, Luna-Zurita L, del Monte G, Bolos V, Melgar P, Arandilla A, Garratt AN, Zang H, Mukouyama YS, Chen H, Shou W, Ballestar E, Esteller M, Rojas A, Perez-Pomares JM, de la Pompa JL (2007) Notch signaling is essential for ventricular chamber development. Dev Cell 12:415–429 [pmid: 17336907]
17.. Heikinheimo M,Scandrett JM,Wilson DB. Localization of transcription factor GATA-4 to regions of the mouse embryo involved in cardiac developmentDev Biol 1994;164:361–373. [doi: 10.1006/dbio.1994.1206]
17.. Heikinheimo M, Scandrett JM, Wilson DB (1994) Localization of transcription factor GATA-4 to regions of the mouse embryo involved in cardiac development. Dev Biol 164:361–373 [pmid: 8045339]
18.. Hoogaars WMH,Tessari A,Moorman AFM,Boer PAJ,Hagoort J,Soufan AT,Campione M,Christoffels VM. The transcriptional repressor Tbx3 delineates the developing central conduction system of the heartCardiovasc Res 2004;62:489–499. [doi: 10.1016/j.cardiores.2004.01.030]
18.. Hoogaars WMH, Tessari A, Moorman AFM, de Boer PAJ, Hagoort J, Soufan AT, Campione M, Christoffels VM (2004) The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart. Cardiovasc Res 62:489–499 [pmid: 15158141]
19.. Hoogaars WMH,Engel A,Brons JF,Verkerk AO,Lange FJ,Wong LYE,Bakker ML,Clout DE,Wakker V,Barnett P,Ravesloot JH,Moorman AFM,Verheijck EE,Christoffels VM. Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atriaGenes Dev 2007;21:1098–1112. [doi: 10.1101/gad.416007]
19.. Hoogaars WMH, Engel A, Brons JF, Verkerk AO, de Lange FJ, Wong LYE, Bakker ML, Clout DE, Wakker V, Barnett P, Ravesloot JH, Moorman AFM, Verheijck EE, Christoffels VM (2007) Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. Genes Dev 21:1098–1112 [pmid: 17473172]
20.. Kamino K,Hirota A,Fujii S. Localization of pacemaking activity in early embryonic heart monitored using voltage-sensitive dyeNature 1981;290:595–597. [doi: 10.1038/290595a0]
20.. Kamino K, Hirota A, Fujii S (1981) Localization of pacemaking activity in early embryonic heart monitored using voltage-sensitive dye. Nature 290:595–597 [pmid: 7219544]
21.. Lints TJ,Parsons LM,Hartley L,Lyons I,Harvey RP. Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendantsDevelopment 1993;119:419–431.
21.. Lints TJ, Parsons LM, Hartley L, Lyons I, Harvey RP (1993) Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants. Development 119:419–431 [pmid: 7904557]
22.. Moorman AFM,Christoffels VM. Cardiac chamber formation: development, genes and evolutionPhysiol Rev 2003;83:1223–1267.
22.. Moorman AFM, Christoffels VM (2003) Cardiac chamber formation: development, genes and evolution. Physiol Rev 83:1223–1267 [pmid: 14506305]
23.. Moorman AFM,Schumacher CA,Boer PAJ,Hagoort J,Bezstarosti K,Hoff MJB,Wagenaar GTM,Lamers JMJ,Wuytack F,Christoffels VM,Fiolet JWT. Presence of functional sarcoplasmic reticulum in the developing heart and its confinement to chamber myocardiumDev Biol 2000;223:279–290. [doi: 10.1006/dbio.2000.9752]
23.. Moorman AFM, Schumacher CA, de Boer PAJ, Hagoort J, Bezstarosti K, van den Hoff MJB, Wagenaar GTM, Lamers JMJ, Wuytack F, Christoffels VM, Fiolet JWT (2000) Presence of functional sarcoplasmic reticulum in the developing heart and its confinement to chamber myocardium. Dev Biol 223:279–290 [pmid: 10882516]
24.. Moorman AFM,Soufan AT,Hagoort J,Boer PAJ,Christoffels VM. Development of the building plan of the heartAnn NY Acad Sci 2004;1015:171–181. [doi: 10.1196/annals.1302.014]
24.. Moorman AFM, Soufan AT, Hagoort J, de Boer PAJ, Christoffels VM (2004) Development of the building plan of the heart. Ann NY Acad Sci 1015:171–181 [pmid: 15201158]
25.. Moorman AFM,Christoffels VM,Anderson RH,Hoff MJB. The heart-forming fields: one or multiple?Phil Trans R Soc B 2007;362:1257–1265. [doi: 10.1098/rstb.2007.2113]
25.. Moorman AFM, Christoffels VM, Anderson RH, van den Hoff MJB (2007) The heart-forming fields: one or multiple? Phil Trans R Soc B 362:1257–1265 [pmid: 17581808]
26.. Patten BM,Kramer TC. The initiation of contraction in the embryonic chicken heartAm J Anat 1933;53:349–375. [doi: 10.1002/aja.1000530302]
26.. Patten BM, Kramer TC (1933) The initiation of contraction in the embryonic chicken heart. Am J Anat 53:349–375
27.. Prall OWJ,Menon MK,Solloway MJ,Watanabe Y,Zaffran S,Bajolle F,Biben C,McBride JJ,Robertson BR,Chaulet H,Stennard FA,Wise N,Schaft D,Wolstein O,Furtado MB,Shiratori H,Chien KR,Hamada H,Black BL,Saga Y,Robertson EJ,Buckingham ME,Harvey RP. An Nkx2–5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferationCell 2007;128:947–959. [doi: 10.1016/j.cell.2007.01.042]
27.. Prall OWJ, Menon MK, Solloway MJ, Watanabe Y, Zaffran S, Bajolle F, Biben C, McBride JJ, Robertson BR, Chaulet H, Stennard FA, Wise N, Schaft D, Wolstein O, Furtado MB, Shiratori H, Chien KR, Hamada H, Black BL, Saga Y, Robertson EJ, Buckingham ME, Harvey RP (2007) An Nkx2–5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. Cell 128:947–959 [pmid: 17350578]
28.. Rana MS,Horsten NCA,Tesink-Taekema S,Lamers WH,Moorman AFM,Hoff MJB. Trabeculated right ventricular free wall in the chicken heart forms by ventricularization of the myocardium initially forming the outflow tractCirc Res 2007;100:1000–1007. [doi: 10.1161/01.RES.0000262688.14288.b8]
28.. Rana MS, Horsten NCA, Tesink-Taekema S, Lamers WH, Moorman AFM, van den Hoff MJB (2007) Trabeculated right ventricular free wall in the chicken heart forms by ventricularization of the myocardium initially forming the outflow tract. Circ Res 100:1000–1007 [pmid: 17347476]
29.. Rawles ME. The heart-forming areas of the early chick blastodermPhysiol Zool 1943;16:22–42.
29.. Rawles ME (1943) The heart-forming areas of the early chick blastoderm. Physiol Zool 16:22–42
30.. Rosenquist GC,Haan RL. Migration of precardiac cells in the chick embryo: a radioautographic study. Carnegie Institute Washington Publ. 625. Contributions to embryology 1966Washington, DC: Carnegie Institute; :111–121.
30.. Rosenquist GC, de Haan RL (1966) Migration of precardiac cells in the chick embryo: a radioautographic study. Carnegie Institute Washington Publ. 625. Contributions to embryology. Carnegie Institute, Washington, DC, pp 111–121
31.. Ruijter JM,Soufan AT,Hagoort J,Moorman AFM. Molecular imaging of the embryonic heart: fables and facts on 3D imaging of gene expression patternsBirth Defects Res C Embryo Today 2004;72:224–240. [doi: 10.1002/bdrc.20018]
31.. Ruijter JM, Soufan AT, Hagoort J, Moorman AFM (2004) Molecular imaging of the embryonic heart: fables and facts on 3D imaging of gene expression patterns. Birth Defects Res C Embryo Today 72:224–240 [pmid: 15495186]
32.. Sabin FR. Studies on the origin of blood vessels and of red blood corpuscules as seen in the living blastoderm of chicks during the second day of incubationContrib Embryol 1920;9:213–262.
32.. Sabin FR (1920) Studies on the origin of blood vessels and of red blood corpuscules as seen in the living blastoderm of chicks during the second day of incubation. Contrib Embryol 9:213–262
33.. Satin J,Bader D,Haan RL. Local cues influence atrial and ventricular differentiation of precardiac mesodermJ Mol Cell Cardiol 1987;19:S16a. [doi: 10.1016/S0022-2828(87)80673-9]
33.. Satin J, Bader D, de Haan RL (1987) Local cues influence atrial and ventricular differentiation of precardiac mesoderm. J Mol Cell Cardiol 19:S16a (abstract)
34.. Satin J,Fujii S,Haan RL. Development of cardiac heartbeat in early chick embryos is regulated by regional cuesDev Biol 1988;129:103–113. [doi: 10.1016/0012-1606(88)90165-0]
34.. Satin J, Fujii S, de Haan RL (1988) Development of cardiac heartbeat in early chick embryos is regulated by regional cues. Dev Biol 129:103–113 [pmid: 3410155]
35.. Schoenebeck JJ,Keegan BR,Yelon D. Vessel and blood specification override cardiac potential in anterior mesodermDev Cell 2007;13:254–267. [doi: 10.1016/j.devcel.2007.05.012]
35.. Schoenebeck JJ, Keegan BR, Yelon D (2007) Vessel and blood specification override cardiac potential in anterior mesoderm. Dev Cell 13:254–267 [pmid: 17681136]
36.. Sissman J. Cell multiplication rates during development of the primitive cardiac tube in the chick embryoNature 1966;210:504–507. [doi: 10.1038/210504a0]
36.. Sissman J (1966) Cell multiplication rates during development of the primitive cardiac tube in the chick embryo. Nature 210:504–507 [pmid: 5960515]
37.. Slack JMW. From egg to embryo. Determinative events in early development. 1983Cambridge: Cambridge University Press;
37.. Slack JMW (1983) From egg to embryo. Determinative events in early development. Cambridge University Press, Cambridge
38.. Soufan AT,Berg G,Ruijter JM,Boer PAJ,Hoff MJB,Moorman AFM. Regionalized sequence of myocardial cell growth and proliferation characterizes early chamber formationCirc Res 2006;99:545–552. [doi: 10.1161/01.RES.0000239407.45137.97]
38.. Soufan AT, van den Berg G, Ruijter JM, de Boer PAJ, van den Hoff MJB, Moorman AFM (2006) Regionalized sequence of myocardial cell growth and proliferation characterizes early chamber formation. Circ Res 99:545–552 [pmid: 16888243]
39.. Soufan AT,Berg G,Moerland PD,Massink MMG,Hoff MJB,Moorman AFM,Ruijter JM. Three-dimensional measurement and visualization of morphogenesis applied to cardiac embryologyJ Microsc 2007;225:269–274. [doi: 10.1111/j.1365-2818.2007.01742.x]
39.. Soufan AT, van den Berg G, Moerland PD, Massink MMG, van den Hoff MJB, Moorman AFM, Ruijter JM (2007) Three-dimensional measurement and visualization of morphogenesis applied to cardiac embryology. J Microsc 225:269–274 [pmid: 17371450]
40.. Srivastava D,Cserjesi P,Olson EN. A subclass of bHLH proteins required for cardiac morphogenesisScience 1995;270:1995–1999. [doi: 10.1126/science.270.5244.1995]
40.. Srivastava D, Cserjesi P, Olson EN (1995) A subclass of bHLH proteins required for cardiac morphogenesis. Science 270:1995–1999 [pmid: 8533092]
41.. Stalsberg H. The origin of heart asymmetry: right and left contributions to the early chick embryo heartDev Biol 1969;19:109–127. [doi: 10.1016/0012-1606(69)90051-7]
41.. Stalsberg H (1969) The origin of heart asymmetry: right and left contributions to the early chick embryo heart. Dev Biol 19:109–127 [pmid: 5775721]
42.. Stalsberg H,Haan RL. The precardiac areas and formation of the tubular heart in the chick embryoDev Biol 1969;19:128–159. [doi: 10.1016/0012-1606(69)90052-9]
42.. Stalsberg H, de Haan RL (1969) The precardiac areas and formation of the tubular heart in the chick embryo. Dev Biol 19:128–159 [pmid: 4180350]
43.. Thompson RP,Lindroth JR,Wong YMM. Clark EB,Takao ARegional differences in DNA-synthetic activity in the preseptation myocardium of the chickDevelopmental cardiology: morphogenesis and function 1990NY: Futura, Mount Kisco; :219–234.
43.. Thompson RP, Lindroth JR, Wong YMM (1990) Regional differences in DNA-synthetic activity in the preseptation myocardium of the chick. In: Clark EB, Takao A (eds) Developmental cardiology: morphogenesis and function. Futura, Mount Kisco, NY, pp 219–234
44.. Tokuyasu KT,Maher PA. Immunocytochemical studies of cardiac myofibrillogenesis in early chick embryos. II. Generation of β-actinin dots within titin spots at the time of the first myofibril formationJ Cell Biol 1987;105:2795–2801. [doi: 10.1083/jcb.105.6.2795]
44.. Tokuyasu KT, Maher PA (1987) Immunocytochemical studies of cardiac myofibrillogenesis in early chick embryos. II. Generation of β-actinin dots within titin spots at the time of the first myofibril formation. J Cell Biol 105:2795–2801 [pmid: 3320056]
45.. van den Berg G, Abu-Issa R, de Boer BA, Hutson MR, de Boer PAJ, Soufan AT, Ruijter JM, Kirby ML, van den Hoff MJB, Moorman AFM (2008) A caudal proliferating growth center contributes to both poles of the forming heart tube. Circ Res. doi: 10.1161/CIRCRESAHA.108.185843
46.. Schulte H von W (1916) The fusion of the cardiac anlages and the formation of the cardiac loop in the cat (felis domestica). Am J Anat 20:45–72
47.. Yoshinaga T. A contribution to the early development of the heart in mammalia, with special reference to the guinea pigAnat Rec 1921;21:239–308. [doi: 10.1002/ar.1090210301]
47.. Yoshinaga T (1921) A contribution to the early development of the heart in mammalia, with special reference to the guinea pig. Anat Rec 21:239–308
48.. Yuan S,Schoenwolf GC. Islet-1 marks the early heart rudiments and is asymmetrically expressed during early rotation of the foregut in the chick embryoAnat Rec 2000;260:204–207. [doi: 10.1002/1097-0185(20001001)260:2<204::AID-AR90>3.0.CO;2-5]
48.. Yuan S, Schoenwolf GC (2000) Islet-1 marks the early heart rudiments and is asymmetrically expressed during early rotation of the foregut in the chick embryo. Anat Rec 260:204–207 [pmid: 10993956]
49.. Zaffran S,Kelly RG,Meilhac SM,Buckingham ME,Brown NA. Right ventricular myocardium derives from the anterior heart fieldCirc Res 2004;95:261–268. [doi: 10.1161/01.RES.0000136815.73623.BE]
49.. Zaffran S, Kelly RG, Meilhac SM, Buckingham ME, Brown NA (2004) Right ventricular myocardium derives from the anterior heart field. Circ Res 95:261–268 [pmid: 15217909]

Figures

[Figure ID: Fig1]
Fig. 1 

Changing view of cardiac development. The illustration on the left shows a heart tube as it was previously often depicted: the straight heart tube containing all cardiac compartments as circumferential segments. The illustrations on the right show the straight heart tube with its revised fate: only precursors of the future left ventricle are present. The hatched lines indicate endocardial cell layers. The continuous lines indicate myocardial cell layers. Source: images are based on Patten and Kramer [26]



[Figure ID: Fig2]
Fig. 2 

Morphological changes during early heart development. The illustrations on the left show how, by folding of the embryo, a foregut (show in green) is formed, and how the bilateral heart-forming region (shown in gray) swings toward ventral and medial to progressively fuse at the midline. The illustrations on the right show schematic transverse sections of the changes that occur in the embryo during folding. AIP anterior intestinal portal, c.c. coelomic cavity, dm dorsal mesocardium, ectod ectoderm, endod endoderm, fg foregut, HFR heart-forming region, lat lateral, med medial, mesod mesoderm, ng neural groove, pbw pericardial back wall, * contact between endocardium and myocardium. Source: images are based on Stalsberg and De Haan [42] and De Jong et al. [9]



[Figure ID: Fig3]
Fig. 3 

The fate of the early heart tube. A summary of experiments by De la Cruz et al. [1214]. The early heart tube was labeled and reincubated. Ventral views of a straight (a) and a looping (b) heart tube. c Right view of a chamber-forming heart. d Ventral view of a four-chambered heart, showing the inflow of the left ventricle (LV) and the outflow of the right ventricle. LA left atrium, PT pulmonary trunk, RA right atrium, RV right ventricle



[Figure ID: Fig4]
Fig. 4 

The ballooning model. A reconstruction of Cx40 expression (shown in blue) in the heart of a mouse ED 9.5. a The entire reconstruction, in bd the OFT is removed. AVC atrioventricular canal, IC inner curvature, LA left atrium, LCV left caval vein, LV left ventricle, OFT outflow tract, PhAA pharyngeal arch arteries, RA right atrium, RCV right caval vein, RV right ventricle



Article Categories:
  • Riley Symposium

Keywords: Keywords Cardiovascular development, Heart fields, Lineage, Proliferation, Morphology.

Previous Document:  Stem cells from in- or outside of the heart: isolation, characterization, and potential for myocardi...
Next Document:  Partial anomalous pulmonary venous drainage in young pediatric patients: the role of magnetic resona...