Asymmetric Cell Divisions Promote Stratification and Differentiation of Mammalian Skin

Nature. 2005 Sep 8;437(7056):275-80. doi: 10.1038/nature03922. Epub 2005 Aug 10.

Abstract

The epidermis is a stratified squamous epithelium forming the barrier that excludes harmful microbes and retains body fluids. To perform these functions, proliferative basal cells in the innermost layer periodically detach from an underlying basement membrane of extracellular matrix, move outward and eventually die. Once suprabasal, cells stop dividing and enter a differentiation programme to form the barrier. The mechanism of stratification is poorly understood. Although studies in vitro have led to the view that stratification occurs through the delamination and subsequent movement of epidermal cells, most culture conditions favour keratinocytes that lack the polarity and cuboidal morphology of basal keratinocytes in tissue. These features could be important in considering an alternative mechanism, that stratification occurs through asymmetric cell divisions in which the mitotic spindle orients perpendicularly to the basement membrane. Here we show that basal epidermal cells use their polarity to divide asymmetrically, generating a committed suprabasal cell and a proliferative basal cell. We further demonstrate that integrins and cadherins are essential for the apical localization of atypical protein kinase C, the Par3-LGN-Inscuteable complex and NuMA-dynactin to align the spindle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation*
  • Cell Division
  • Cell Polarity*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Dynactin Complex
  • Epidermal Cells
  • Epidermis / metabolism
  • Immunoprecipitation
  • Integrins / metabolism
  • Keratins / genetics
  • Keratins / metabolism
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Mitosis
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Kinase C / metabolism
  • Receptors, Thrombin / metabolism
  • Skin / cytology*
  • Skin / metabolism*
  • Spindle Apparatus / metabolism

Substances

  • Cadherins
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Dynactin Complex
  • Integrins
  • Microtubule-Associated Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Numa1 protein, mouse
  • Receptors, Thrombin
  • fat1 protein, mouse
  • protease-activated receptor 3
  • Keratins
  • PKC-3 protein
  • Protein Kinase C