Abstract

Pseudostratified epithelia (PSE) are a common type of columnar epithelia found in a wealth of embryonic and adult tissues such as ectodermal placodes, the trachea, the ureter, the gut and the neuroepithelium. PSE are characterized by the choreographed displacement of cells' nuclei along the apicobasal axis according to phases of their cell cycle. Such movements, called interkinetic movements (INM), have been proposed to influence tissue expansion and shape and suggested as culprit in several congenital diseases such as CAKUT (Congenital anomalies of kidney and urinary tract) and esophageal atresia. INM rely on cytoskeleton dynamics just as adhesion, contractility and mitosis do. Therefore, long term impairment of INM without affecting proliferation and adhesion is currently technically unachievable. Here we bypassed this hurdle by generating a 2D agent-based model of a proliferating PSE and compared its output to the growth of the chick neuroepithelium to assess the interplay between INM and these other important cell processes during growth of a PSE. We found that INM directly generates apical expansion and apical nuclear crowding. In addition, our data strongly suggest that apicobasal elongation of cells is not an emerging property of a proliferative PSE but rather requires a specific elongation program. We then discuss how such program might functionally link INM, tissue growth and differentiation.

Highlights

  • Pseudostratified epithelia (PSE) are a special type of columnar epithelia in which cells are thin and elongated

  • interkinetic nuclear movements (INM) rely on cytoskeleton dynamics just as adhesion, contractility and mitosis do

  • INM are decomposed in several steps: an apical to basal movement occurring during the G1 and S phases of the cell cycle and a basal to apical nuclear movement occurring during the G2 and M phases

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Summary

Introduction

Pseudostratified epithelia (PSE) are a special type of columnar epithelia in which cells are thin and elongated. The apicalward movement, sometimes referred to as PRAM (Pre-mitotic Rapid Apical Movement), can be achieved via microtubules like in the chick neuroepithelium [5] or in the brain of mouse and rat embryos [6, 7] as well as in the retina of post-natal mice [8]. In ferrets’ brains apical to basal movements of nuclei are faster than basal to apical movements suggesting that the nuclear movement towards basal regions of the brain is active while the opposite is observed in mouse [11] All these observations indicate that INM are regulated by cytoskeleton-dependent mechanisms and that the actual mechanism employed differs from species to species and organ to organ

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