Trabeculation in the embryonic heart

Abstract

We have read with interest the recent r e v i e w~( I ,~,~) drawing the attention of a wider audience to the process of trabeculation during embryonic heart morphogenesis. Whilst welcoming this, we are concerned that some of what has been written could be confusing and misleading to a reader not familiar with embryonic hearts.Trabeculation is a morphogenetic process undergone by the luminal side of some parts of the myocardium (muscle wall) of the developing vertebrate heart. We think that the structure of trabeculated myocardium is not well described by 'finger-like projections' as is often used (e.g. as in refs 1,2 and 3). Trabeculated embryonic ventricular myocardium more resembles sheets or a sponge-like structure (e.g. as in refs 4 3 , with no free 'finger-tips'. Although some cross-sectional views can look consistent with finger-or villus-like outgrowths, more careful examination, scanning electron microscopy (e.g. as in refs 4 and 5), confocal microscopy or three-dimensional reconstruction techniques clearly demonstrate its real nature.A second point of confusion is the idea that trabeculation is confined to the ventricular myocardium. This is not the case. Atrial myocardium also becomes 'trabeculated', forming a leaf vein-like structure@) on the luminal side of the wall. This process commences slightly later than in the ventricles -too late to have occurred (or not) in the hearts of 'knockout' mice, in which ventricular trabeculation is severely compromised by the absence of neuregulin or some of its receptor (reviewed in refs 1 and 2).There are various hypotheses about functions of trabeculation: to provide sufficient pumping function during growth and allow for nutrition of embryonic myocardium before coronary vascularisation (reviewed by ref. 7), and to separate blood currents in the pre-septation heart@). Myocardial architecture, particularly in the ventricle, undergoes considerable changes during embryonic and fetal development. Some trabeculated myocardium remains both in the ventricles (including as papillary muscles supporting the atrioventricular valve leaflets) and in the atria (as pectinate muscles) of the mature heart@).Knowledge and understanding of the molecular mechanisms underlying development are becoming increasingly detailed. For the most rapid advances of this type to be made in morphogenesis, we would like to encourage a similar degree of attention with respect to knowledge, under-Fig. 1. Scanning electron micrograph of a transverse slice through an embryonic chick heart (day 5 of incubation, HH stage 27), showing the abundant, sponge-like trabecular meshwork in the basal part of the right ventricle (RV) and developing pectinate muscles in the left atrium (LA).standing and accurate communication of the morphology of the developing tissue itself.

GATA4 is essential for formation of the proepicardium and regulates cardiogenesis

“…Defects in trabeculation are a feature of other mouse mutants, including Nkx2-5, Raldh2, and Mef2c, which result in developmental arrest between E9.5 and E10.5 (20)(21)(22). This may reflect the role of trabeculae in adding contractile power to the ventricles at this stage in development (23).…”

Convergent proliferative response and divergent morphogenic pathways induced by epicardial and endocardial signaling in fetal heart development

“…The compact zone becomes morphologically recognizable around E11.5, and continues to expand throughout gestation. It is believed that the trabecular myocardium provides most of the contractile force of the early heart, although this function is supplanted by the compact zone myocardium as the latter expands in size (Sedmera and Thomas, 1996). Thus, mouse mutants in which trabecular formation is compromised die around E10.5, whereas those in which compact zone formation is impeded die around E14.5.…”

IGF signaling directs ventricular cardiomyocyte proliferation during embryonic heart development

“…Starting at ~E10.5, immediately following the formation of the epicardium, the myocardium in the ventricular chamber expands significantly by cell proliferation and becomes partitioned into two distinct subdomains: trabecular myocardium facing the endocardium, and compact zone myocardium facing the epicardium. Compact zone myocardium is destined to form the ventricular wall, which provides the bulk of the force of ventricular contraction starting from midgestation (Sedmera and Thomas, 1996).…”