Mechanisms of Trabecular Formation and Specification During Cardiogenesis

Abstract

Trabecular morphogenesis is a key morphologic event during cardiogenesis and contributes to the formation of a competent ventricular wall. Lack of trabeculation results in embryonic lethality. The trabecular morphogenesis is a multistep process that includes, but not limited to, trabecular initiation, proliferation/growth, specification and compaction. Although a number of signaling molecules have been implicated in regulating trabeculation, the cellular processes underlying mammalian trabecular formation are not fully understood. Recent works show that the myocardium displays polarity, and oriented cell division and directional migration of the cardiomyocytes in the monolayer myocardium are required for trabecular initiation and formation. Furthermore, perpendicular oriented cell division is an extrinsic asymmetric cell division that contributes to trabecular specification, and is a mechanism that causes the trabecular cardiomyocytes to be distinct from the cardiomyocytes in compact zone. Once the coronary vasculature system starts to function in the embryonic heart, the trabeculae will coalesce with the compact zone to thicken the heart wall, and abnormal compaction will lead to left ventricular non-compaction (LVNC) and heart failure. There are many reviews about compaction and LVNC. In this review, we will focus on the roles of myocardial polarity and oriented cell division in trabecular initiation, formation, and specification.

Filamentous nestin and nonmuscle myosin IIB are associated with a migratory phenotype in neonatal rat cardiomyocytes

“…In the embryonic zebrafish heart, a subpopulation of cardiomyocytes residing in the compact myocardium begin to extend distinct protrusions before a directional migration into the trabecular layer leading to trabeculae formation (Liu et al, 2010; Staudt et al, 2014). A similar paradigm was reported in the mammalian embryonic heart as trabecular formation involves the directional migration of a subpopulation of cardiomyocytes that undergo cytoskeleton rearrangement, become elongated, orient perpendicular to the compact myocardium, and migrate into the cardiac jelly (Samsa et al, 2013; Wu, 2018). Two independent studies reported that nestin was expressed in mouse embryonic cardiomyocytes during cardiogenesis and the present study revealed that de novo nestin expressed in NNVMs was associated with a migratory phenotype (Meus et al, 2017; Kachinsky et al, 1995).…”

“…The migration of mononucleated cardiomyocytes also constitutes a prerequisite event during the formation of the embryonic heart. In the embryonic zebrafish and mammalian heart, trabecular formation was initiated by cardiomyocytes that undergo cytoskeleton rearrangement, become elongated, orient perpendicular to the heart wall, and eventually migrated into the cardiac jelly (Liu et al, 2010; Samsa, Yang, & Lui, 2013; Staudt et al, 2014; Wu, 2018). In the embryonic zebrafish heart, several studies have reported that before trabeculae formation, cardiomyocytes begin to extend distinct protrusions (Liu et al, 2010; Staudt et al, 2014).…”

“…cytoskeleton rearrangement, become elongated, orient perpendicular to the heart wall, and eventually migrated into the cardiac jelly (Liu et al, 2010;Samsa, Yang, & Lui, 2013;Staudt et al, 2014;Wu, 2018).…”

Functional Morphology of the Cardiac Jelly in the Tubular Heart of Vertebrate Embryos

“…The second concept of the formation of myocardial trabeculae describes the emergence and expansion of the trabecular layer of the embryonic ventricles as a centripetal growth process [100,113,116,117,118]. This means that the myocardial trabeculae are suspected to elongate by inward growth toward the centers of the embryonic ventricles (see Figure 3 in [100], Figure 3 in [116], and Figure 1 in [117]).…”

Functional Morphology of the Cardiac Jelly in the Tubular Heart of Vertebrate Embryos

“…1 in [112]). This inward growth is suspected to result either from a buckling process [95] or from the translocation of ventricular cardiomyocytes (by directional cell migration and oriented cell divisions) into non-removed CJ between the endocardial projections of the trabecular shields [reviewed by Wu 2018]. The latter mechanistic concept suggests that the CJ might act as a physical route for the ingrowth of myocardial trabeculae.…”