Scutoids unveil the three-dimensional packing in curved epithelia

Abstract

As animals develop, the initial simple planar epithelia of the early embryos must acquire complex three-dimensional architectures to form the final functional tissues of the organism. Epithelial bending is, therefore, a general principle of all developing systems. Scholarly publications depict epithelial cells as prisms where their basal and apical faces resemble polygons with the same number of sides. The accepted view is that, when a tissue bend, the cells of the epithelia modify their shape from columnar to what has been traditionally called “bottle shape”. However, the morphology and packing of curved epithelia remain largely unknown. Here, through mathematical and computational modelling, we show that cells in bent epithelia necessarily undergo intercalations along the apico-basal axis. This event forces cells to exchange their neighbours between their basal and apical surfaces. Therefore, the traditional view of epithelial cells as simple prisms is incompatible with this phenomenon. Consequently, epithelial cells are compelled to adopt a novel geometrical shape that we have named “scutoid”. The in-depth analysis of diverse epithelial tissues and organs confirm the generation of apico-basal transitions among cell during morphogenesis. Using biophysics arguments, we determine that scutoids support the energetic minimization on the tissue and conclude that the transitions along the apico-basal axis stabilize the threedimensional packing of the tissue. Altogether, we argue that scutoids are nature’s solution to bend efficiently epithelia, and the missing piece for developing a unifying and realistic model of epithelial architecture.