**2. Gene expression**

In mammals, 23% of cardiac-specific genes show differences in expression between the atria and the ventricle [3]. Key morphogenetic events during heart ontogenesis are conserved

© 2013 Genge et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Genge et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

across vertebrates [4]. Gene expression programs specific to each chamber are likely regulat‐ ing key aspects of chamber formation. The focus on fish heart developmental patterns has primarily been due to the use of zebrafish as a model organism of vertebrate development. The morphological differences created during chamber development are guided by changes in gene expression patterns [1], a process well conserved in vertebrates, regardless of wheth‐ er there are one or two atria or ventricles. Genetic screens in zebrafish have revealed genes and pathways underlying development in the heart. Since many stages of development are conserved across vertebrates, this information has generated considerable insight into con‐ genital heart defects in humans. In the context of this chapter, timing and localization of gene expression can also contribute to our understanding of the differentiation of chambers both in morphology as well as through variation in contractility.

tion requires appropriate relative sizes of the atrium and ventricle. Bone morphogenetic pro‐ tein (BMP) signaling has been shown to be involved with the regulation of chamber size in zebrafish [12]. However, mutations affecting BMP signaling only reduce atrium size but not the ventricle. During this stage of development, the size of chambers may be relatively inde‐

Functional and Structural Differences in Atria Versus Ventricles in Teleost Hearts

http://dx.doi.org/10.5772/53506

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In fish the heart is arranged in series with the ventricle primarily filled by contraction of the atrium [13], rather than the mammalian system in which the thin-walled atrium con‐ tributes only a small amount to ventricular filling under resting conditions. While the at‐ rium and ventricle compose the main muscular components of the fish heart, there are other chambers with important roles in guiding appropriate blood flow through the heart. Generally in fish blood flows through the sinus venosus to the atrium to the ventricle and then out to the bulbus anteriosus. More recently, the atrioventricular region and conus ar‐ teriosus have been identified as morphologically discrete segments present throughout

As with most vertebrates, the cardiac tube is S-shaped with a dorsally positioned atrium and ventrally positioned ventricle to allow for appropriate momentum of the bloodstream to‐ wards the arterial pole. The morphology of the heart sets up an alternating arrangement of slow conducting segments (e.g. inflow tract, atrioventricular region and outflow tract) with fast conducting contractile segments (atrium and ventricle). Blood first enters the thin-wal‐ led sinus venosus. This is an independent, but non-muscular chamber in fish that acts as a drainage pool for the venous system. The composition of the sinus venosus varies greatly between species, from primarily connective tissue in *Danio rerio* (zebrafish) to mainly myo‐ cardium in *Anguilla anguilla* (European eel) to even smooth muscle cells in *Cyprinus carpio* (carp) [16, 17, 18]. The presence of the sinus venosus has thus been suspected to have al‐ lowed the development of the atrium as the principal driving force for ventricular filling [19]. Blood then moves into the atrium, an active contractile chamber in fish that again shows considerable variability in size and shape between species [18]. A general trend throughout teleost species is the similarity in volume of the two main muscular chambers is indicative of the importance of the role of the atrium in filling the ventricle. While atrial vol‐ ume is closer in size to that of the ventricle in fish, the atrium is still less developed muscu‐

Separating the atrium and the ventricle is the atrioventricular region, a ring of cardiac tissue supporting the AV valves. The degree of isolation of this region from the surrounding mus‐ culature varies between species [23] but in all species it plays a critical role in regulating the pattern of electrical conduction. The ventricle has a mass and wall thickness up to five times that of the atrium [18]. The thickly muscular ventricle varies in terms of structural organiza‐

larly and possibly representative of a more primitive heart [20-22].

pendent of one another.

modern teleosts as well [14, 15].

**3.1 General morphology**

**3. Morphology**

The T-box genes (Tbx) are responsible, in large part, for patterning that distinguishes cham‐ ber myocardium from non-chamber myocardium [5]. Subregionalization is important for at‐ rial or ventricular identity, either via selective transcription or repression of genes. The physical interaction of Nkx2.5, Gata4 and Tbx5 in particular activates the expression of chamber-specific genes to stimulate the differentiation of primary myocardial cells into chamber myocardium [1]. By the time cells are restricted to cardiac lineage, they are already destined for either the atrium or the ventricle. During early gastrulation, myocardial pro‐ genitors already have axial coordinates that lead to chamber assignment [6]. There are two sources of these myocardial progenitors, or two heart fields. In the first heart field, cardio‐ myocyte differentiation initiates in the ventricle and allows continuous addition of new car‐ diomyocytes to the venous pole of the heart tube progressing towards the atrium [7]. Differentiation at the arterial pole in the second heart field occurs only in the later stages of cardiac development. By 72 hours post-fertilization (hpf) individual heart chambers are morphologically differentiated with the ventricular wall being thicker and ventricular cardi‐ omyocytes being larger than those of the atrium [8].

The chambers express different subsets (or paralogs) of sarcomeric proteins such as myosin heavy chains (MHC) and myosin light chains (MLC) [9]. Variation in paralog expression (frequently referred to in the literature as isoforms) may confer differing contractile proper‐ ties to the atrium and the ventricle, such as with altered MHC expression being correlated with altered myofibrillar ATPase activity (crucian carp - [10]). MHC expression is chamberspecific by 22 hpf, preceding any obvious chamber formation but corresponding to the ini‐ tiation of the heart beat [6]. These isoforms are not only divided spatially but also by differences in timing of expression. Atrial-specific myosin gene expression is induced after ventricle-specific myosin gene expression in zebrafish [11]. This time-dependent expression may be due to repression of the promoters of these genes [1].

The timing of these developmental pathways is critical, as the development of one chamber can influence the other. Ventricular morphology can change with developmental atrial dys‐ function seen with zebrafish mutations in atrial-specific MHC [11]. For example, in the wea mutant, a lack of a functional atrial MHC results in defects in atrial myofilament organiza‐ tion and contractility. Despite the mutation being seen only in a chamber-specific protein, the ventricle changes as well in response to these atrial defects. Effective embryonic circula‐ tion requires appropriate relative sizes of the atrium and ventricle. Bone morphogenetic pro‐ tein (BMP) signaling has been shown to be involved with the regulation of chamber size in zebrafish [12]. However, mutations affecting BMP signaling only reduce atrium size but not the ventricle. During this stage of development, the size of chambers may be relatively inde‐ pendent of one another.
