Epithelial Folding: How Planar Cell Polarity Regulates 3D Organogenesis

BPJ_111_3.c1.inddIt is a nice season to enjoy the river by canoeing or kayaking. But do you know that mammalian eggs also drift over a deep channel? This channel, or epithelial folds, is in a tubular organ named the oviduct, or Fallopian tube in humans, connecting the ovary and the uterus.

Viewing the cover image, you too can experience going through the oviduct from the point of view of an egg. The epithelium of the oviduct in the image was obtained by a mathematical simulation. The epithelial folds are straight and align longitudinally along the ovarian-uterine axis in mice and other species of animals. Previously, we reported that a Planar Cell Polarity (PCP) factor Celsr1 regulates fold patterning in mice. But the mechanisms connecting PCP with the well-patterned alignment of the epithelial folds are still unknown.

Here, we analyzed the mechanical regulation of the epithelial fold patterning by mathematical modeling where the epithelium was defined as an elastic sheet. We found that PCP could mechanically regulate the three-dimensional morphogenesis via the polarized cell array. Furthermore, our model scheme is also useful for analyzing mechanical effects on epithelial morphology generally. Our simulation could recapitulate the morphology of various types of epithelial folds, some of which can be found in other organs in vivo.

A sophisticated three-dimensional morphology is important for the organ’s function, but we are still far from a comprehensive understanding of the mechanism to build it.  The oviduct is not only where we come from, but is also a good place to start our scientific journey.

-Dongbo Shi, Hiroshi Koyama, Toshihiko Fujimori


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