Cadherin-mediated cell-cell contact regulates keratinocyte differentiation

Joseph L. Charest, Jean M. Jennings, William P. King, Andrew P. Kowalczyk, Andrés J. García

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Cell-extracellular matrix (ECM) and cell-cell interactions regulate keratinocyte cell fate and differentiation. In the present analysis, we examined the differentiation of primary human keratinocytes cultured on micropatterned substrates that varied the extent of cell-cell contact while maintaining constant cell-ECM areas. Bowtie-shaped micropatterned areas (75-1600 μm 2) were engineered to either permit or prevent cell-cell contact for pairs of adherent keratinocytes. Cell pairs with direct cell-cell contact exhibited enhanced expression of the differentiation markers involucrin and keratin 10 compared to cells with no cell-cell contact. In contrast, available cell-spreading area, as regulated by pattern size, did not alter keratinocyte involucrin expression. Disruption of E-cadherin binding by either antibody blocking or expression of a dominant-negative receptor diminished the ability of micropattern-regulated cell-cell contact to modulate involucrin expression. These results demonstrate that cadherin-mediated cell-cell contact regulates early keratinocyte differentiation independently from changes in cell shape.

Original languageEnglish (US)
Pages (from-to)564-572
Number of pages9
JournalJournal of Investigative Dermatology
Issue number3
StatePublished - Mar 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


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