The development of the heart, the first organ to form during vertebrate development, begins as a simple tube consisting of an outer layer of myocardium and an inner layer of endocardium, separated by an acellular matrix known as cardiac jelly. In mice, this tube begins to beat around embryonic day (E) 8, and within just a couple of days, it elongates, loops and expands into a four-chambered heart. This remarkable transformation relies on precise and highly coordinated cellular communication, and any disruption can have severe consequences.
A long-standing question has been how cells communicate across the cell-free cardiac jelly. Although diffusion of signaling molecules was initially thought to mediate this communication, researchers in Mingfu Wu’s lab at the University of Houston in Texas, USA, questioned whether diffusion alone could deliver the speed and spatial precision necessary for early heart development. “Our thinking changed when we encountered reports of tunneling nanotubes in cultured mammalian cells, long-range filopodia in flies, and cytonemes in flies, which can mediate long-distance transport of signaling molecules”, says Wu. “These studies inspired us to investigate whether a similar microstructure might exist in the developing heart to bridge the endocardium and myocardium”. In their recent study, published in Science, Miao et al. show that that during trabeculation of the cardiac tube, cardiomyocytes and endocardial cells form narrow tunneling nanotube-like structures (TNTLs) across the cardiac jelly during trabeculation, a key phase in heart morphogenesis, to enable direct, rapid and spatially precise communication between the two cell layers.
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