Mechanisms of epithelial packing in proliferative tissues

Abstract

Tissue morphogenesis is intimately linked with the complex changes that occur in the shape and organization of individual cells. In curved epithelia, cells possess the capacity to intercalate along their own apico-basal axes adopting a distinct shape named “scutoid”. This conformation facilitates the minimization of energy within the tissue. However, despite to the association of several geometric and biophysical factors with this 3D reorganisation, the dynamic changes underlying scutoid formation remain poorly understood. To better understand this complex phenomenon, we use live-imaging of a spheroidal epithelium, the sea star embryo, coupled with deep learning-based segmentation, to dissect the relative contributions of cell density, tissue compaction, and cell proliferation on epithelial architecture. Taking advantage of this model system we have performed physical compression experiments to identify cell density as the factor promoting scutoid formation at a global level. We also find that tissue compaction, which naturally occurs in the embryo, is necessary for the appearance of scutoids and their formation tends to be more frequent in highly compacted regions. Finally, when comparing wildtype and compressed embryos with computational models, it becomes evident that tissue compaction and cell density is not sufficient to explain the high incidence of scutoids in a developing epithelium. Therefore, we explore the role of dynamic factors as local cell division throughout the tracking of individual cells. The results indicate most cells acquiring the “scutoidal” shape do so shortly after cell division potentially helping in the accommodation of the new cells within the tissue after the local increase of cell density. In conclusion, the induction of apico-basal intercalations in the sea star embryo might be an efficient way to address the increasing pressure on the tissue at both local and global levels. We propose that proliferation in a compact epithelium induces 3D cell rearrangements during development.