Mendjan Sasha, Deyett Alison, Yelon Deborah
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
Division of Cell Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.
Nat Rev Mol Cell Biol. 2025 Sep 24. doi: 10.1038/s41580-025-00878-5.
Heart development has been extensively explored on the anatomical, cellular and molecular levels. Yet, the intricate interplay of tissue organization, cellular lineages and molecular factors that orchestrate heart development, culminating in forming a seamlessly synchronized functional heart, remains challenging to investigate. Mechanistic studies conducted both in vivo using animal models and in vitro stem-cell-derived systems aim to unravel this complexity. In this Review, we discuss how the recent surge in technological advancements in imaging and genomics, coupled with the evolution of next-generation cardiac organoid models, has provided profound insights into these processes, holding significant implications for the development of novel therapies for congenital or acquired heart diseases. We discuss the development of the heart as the first functional organ - from the morphogenesis of the mesoderm, heart tube and cardiac chambers to the establishment of the initial heartbeat and pacemaker and further how morphogenesis and function collaboratively drive heart maturation.