Planar cell polarity effector gene Intu regulates cell fate-specific differentiation of keratinocytes through the primary cilia

Cell Death Differ. 2013 Jan;20(1):130-8. doi: 10.1038/cdd.2012.104. Epub 2012 Aug 31.

Abstract

Genes involved in the planar cell polarity (PCP) signaling pathway are essential for a number of developmental processes in mammals, such as convergent extension and ciliogenesis. Tissue-specific PCP effector genes of the PCP signaling pathway are believed to mediate PCP signals in a tissue- and cell type-specific manner. However, how PCP signaling controls the morphogenesis of mammalian tissues remains unclear. In this study, we investigated the role of inturned (Intu), a tissue-specific PCP effector gene, during hair follicle formation in mice. Tissue-specific disruption of Intu in embryonic epidermis resulted in hair follicle morphogenesis arrest because of the failure of follicular keratinocyte to differentiate. Targeting Intu in the epidermis resulted in almost complete loss of primary cilia in epidermal and follicular keratinocytes, and a suppressed hedgehog signaling pathway. Surprisingly, the epidermal stratification and differentiation programs and barrier function were not affected. These results demonstrate that tissue-specific PCP effector genes of the PCP signaling pathway control the differentiation of keratinocytes through the primary cilia in a cell fate- and context-dependent manner, which may be critical in orchestrating the propagation and interpretation of polarity signals established by the core PCP components.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Polarity / genetics*
  • Cilia / genetics*
  • Epidermal Cells
  • Epidermis / metabolism
  • Hair Follicle / cytology
  • Hair Follicle / physiology
  • Keratinocytes / cytology*
  • Keratinocytes / physiology*
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Transgenic
  • Signal Transduction

Substances

  • Membrane Proteins
  • inturned protein, mouse