An Appreciation of Anatomy in the Molecular World

Abstract

Robert H. Anderson is one of the most important and accomplished cardiac anatomists of the last decades, having made major contributions to our understanding of the anatomy of normal hearts and the pathologies of acquired and congenital heart diseases. While cardiac anatomy as a research discipline has become largely subservient to molecular biology, anatomists like Professor Anderson demonstrate anatomy has much to offer. Here, we provide cases of early anatomical insights on the heart that were rediscovered, and expanded on, by molecular techniques: migration of neural crest cells to the heart was deduced from histological observations (1908) and independently shown again with experimental interventions; pharyngeal mesoderm is added to the embryonic heart (1973) in what is now defined as the molecularly distinguishable second heart field; chambers develop from the heart tube as regional pouches in what is now considered the ballooning model by the molecular identification of regional differentiation and proliferation. The anatomical discovery of the conduction system by Purkinje, His, Tawara, Keith, and Flack is a special case because the main findings were never neglected in later molecular studies. Professor Anderson has successfully demonstrated that sound knowledge of anatomy is indispensable for proper understanding of cardiac development.

Keywords: cardiac conduction system; cardiac structure; heart development.

Figure 1

Neural crest cells migrating down the pharyngeal arches of a stage 33 embryonic Australian lungfish. Transparent overlay paper was used in this description from 1908 to show the migration (black ovals in right-hand image represent the positions of neural crest cells). Photographed from [8].

Figure 2

Building plan of the heart. (a) Keith and Flack [30] developed a “generalized” scheme of the vertebrate heart where the primitive parts (1,b,3,4,5) form a single domain (although their scheme is much inspired by the formed fish heart in which it is often the case that the atrioventricular part (3,4) is separated from the conal or bulbar valve area (5) by chamber myocardium). (b) The scheme of the cardiac conduction system by Benninghoff [31] is highly similar to that of (a) and while the labels a–d and 1,3,4 are inserted by us such that they correspond to (a), the primitive parts (1,b,3,4) still form a single domain. (c) Benninghoff [31], when conceptualizing the development of the conduction system from a comparative perspective (and maintaining that ectotherms do not have a conduction system comparable to that found in mammals and birds), emphasized the “Ostienringe” (1,3,5) as the precursors of future (“künftigen”) chamber junctions. Although this is still compatible with the ballooning model [29], the depiction of the junctions as entirely separate from each other (1,3,5) was perpetuated (d) to mean that everything between, for example, junctions 1 and 3 would be atrium, whereas Benninghoff’s model (c) does not exclude the presence of an “auricular canal” (label b in (a,b)), or remnant of the primary heart tube. (d) The segmented model presumes that parts b and 4 are lost and the precursors of all segments of the adult heart are present at the heart tube stage, which is therefore in conflict with the addition of cells from the second heart field, the “generalized” scheme (a) and the ballooning model (e) [29]. Image (a) is adapted from [30], (b,c) from [31], and (d) from [32].

Figure 3

Growth of the cardiac ventricle (dashed red line) from a proportionally very trabeculated stage (14) to the end of embryonic development where compaction is presumed to have taken place (23) compared to the superior-lateral papillary muscle of the adult heart (which develops from embryonic trabeculae). From Carnegie stages 14 to 23, the volume of trabecular muscle increases approximately an order of magnitude [85] and then approximately five orders of magnitude to reach 10 g in the adult heart [69] (note that [85] included the ventricular septum in the volume of trabeculae and the numbers we show are a bit lower than in [85]). Images of embryos are adapted from Hill, M.A. (1 September 2020) Embryology Embryonic Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Embryonic_Development.

Figure 4

The atrial septum. (a) The atrial septum of the heart of an adult human exposed by a cut through the intercaval (sinus venarum) area. The thick black line indicates the part of the posterior-superior part of the septum that was sectioned with histology. (b) Histology showing the fold in the atrial roof (a very similar setting has been demonstrated in pig, for example [102,103]). (c,d) Schematic representations of the atrial septum of perinatal stages, with the secondary septum in red. Notice that the fold in the atrial roof is not cartooned. Adapted from [104,105]. (e) Example of schematic that makes a compromise between fold and septum, adapted from [106]. (f,g) Histology of reptiles showing a secondary septum-like aggregate of trabecular muscle in the right atrium of a skink ((f) horizontal section) and a turtle ((g) transverse section), adapted from [107].