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

Elife. 2019 Jun 12:8:e47102. doi: 10.7554/eLife.47102.


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.

Keywords: cell geometry; developmental biology; epidermis; mouse; oriented cell division; planar cell polarity; regenerative medicine; skin; stem cells; stratification.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Division
  • Cell Lineage
  • Cell Polarity
  • Cell Shape
  • Embryo, Mammalian / metabolism
  • Epidermal Cells / cytology
  • Epidermis / embryology*
  • Epithelium / anatomy & histology*
  • Mammals / embryology*
  • Mice, Inbred C57BL
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Tube / pathology
  • Spindle Apparatus / metabolism*
  • Stem Cells / cytology*


  • Ltap protein, mouse
  • Nerve Tissue Proteins