Epithelial geometry regulates spindle orientation and progenitor fate during formation of the mammalian epidermis.

Kimberly Box,Danelle Devenport,Bradley W Joyce

doi:10.7554/elife.47102

Abstract

The control of cell fate through oriented cell division is imperative for proper organ development. Basal epidermal progenitor cells divide parallel or perpendicular to the basement membrane to self-renew or produce differentiated stratified layers, but the mechanisms regulating the choice between division orientations are unknown. Using time-lapse imaging to follow divisions and fates of basal progenitors, we find that mouse embryos defective for the planar cell polarity (PCP) gene, Vangl2, exhibit increased perpendicular divisions and hyperthickened epidermis. Surprisingly, this is not due to defective Vangl2 function in the epidermis, but to changes in cell geometry and packing that arise from the open neural tube characteristic of PCP mutants. Through regional variations in epidermal deformation and physical manipulations, we show that local tissue architecture, rather than cortical PCP cues, regulates the decision between symmetric and stratifying divisions, allowing flexibility for basal cells to adapt to the needs of the developing tissue.

Highlights

Oriented cell division is a fundamental mechanism through which multicellular organisms build complex tissue architecture (Bergstralh et al, 2017; Gillies and Cabernard, 2011)
We explored the possibility that the observed increase in oblique/perpendicular divisions and asymmetric cell fates in Vangl2Lp/Lp mutants is caused by more frequent apical LGN localization
By live imaging of the developing epidermis, we have shown that the orientation of cell division within the skin’s basal progenitor layer is closely linked to the positional fate of daughter cells

Summary

Introduction

Oriented cell division is a fundamental mechanism through which multicellular organisms build complex tissue architecture (Bergstralh et al, 2017; Gillies and Cabernard, 2011). By controlling the angle of the mitotic spindle, a cell can position its daughters to facilitate tissue expansion, establish multiple cell layers, or generate asymmetric cell fates. Unlike simple epithelia, which divide exclusively within the epithelial plane, cells of the innermost, basal layer of the epidermis divide in both planar and perpendicular orientations (Lechler and Fuchs, 2005; Poulson and Lechler, 2010; Smart, 1970). Oriented cell divisions generate one basal and one suprabasal daughter cell that goes on to differentiate and contribute to stratification of the tissue. Cell divisions that occur parallel to the epithelial plane generate two basal daughters, which facilitates tissue growth and expansion of the basal progenitor pool (Ray and Lechler, 2011).

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