Rhythms of growth: unveiling the mechanobiology behind heart maturation

The physiological function of the heart depends on highly coordinated cellular communication, especially during cardiogenesis, when changes in blood flow, extracellular matrix components, and contraction actively drive chamber remodelling. These changes are modulated by cellular behaviour to establish growth for cardiac developmental structure and function. One key to these processes is mechanotransduction, which is the ability of cells to sense and respond to mechanical stimuli. Mechanical cues influence the dynamic expression of genes at each embryonic stage, which plays a critical role in regulating cell migration, differentiation, proliferation, and maturation. In this review, we correlate the mechanobiology of the growing heart with the ability of the nucleus to sense mechanical strain and thereby influence gene expression and cell fate. We examine established roles of signalling pathways and gene expression changes during heart development, while highlighting gaps in our understanding of these complex processes. Considering the mechanosensitive effects of nuclear proteins in translating complex instructions to the nuclear lamina, thereby influencing chromatin states and transcription factor activity, we propose that the exploration of nuclear lamina interactions on chromatin regulation during cardiogenesis holds great potential to drive groundbreaking advances in cardiac research. Thus, the study of mechanotransduction during cardiogenesis may provide a deeper understanding of the transcriptional mechanisms underlying heart formation, including insights into both regeneration and maturation processes.