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

TitleEpithelial geometry regulates spindle orientation and progenitor fate during formation of the mammalian epidermis.
Publication TypeJournal Article
Year of Publication2019
AuthorsBox, K, Joyce, BW, Devenport, D
JournalElife
Volume8
Date Published2019 Jun 12
ISSN2050-084X
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.

DOI10.7554/eLife.47102
Alternate JournalElife
PubMed ID31187731
PubMed Central IDPMC6592681
Grant ListT32GM007388 / / National Institutes of Health /
R01AR068320 / / National Institutes of Health /
AR8472471 / / National Institutes of Health /
R01 AR068320 / AR / NIAMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States