Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts

Linda Schneider, Michael Cammer, Jonathan Lehman, Sonja K. Nielsen, Charles F. Guerra, Iben R. Veland, Christian Stock, Else K. Hoffmann, Bradley K. Yoder, Albrecht Schwab, Peter Satir, Søren T. Christensen

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147 Scopus citations

Abstract

Cell motility and migration play pivotal roles in numerous physiological and pathophysiological processes including development and tissue repair. Cell migration is regulated through external stimuli such as platelet-derived growth factor-AA (PDGF-AA), a key regulator in directional cell migration during embryonic development and a chemoattractant during postnatal migratory responses including wound healing. We previously showed that PDGFRα signaling is coordinated by the primary cilium in quiescent cells. However, little is known about the function of the primary cilium in cell migration. Here we used micropipette analysis to show that a normal chemosensory response to PDGF-AA in fibroblasts requires the primary cilium. In vitro and in vivo wound healing assays revealed that in ORPK mouse (IFT88 Tg737Rpw ) fibroblasts, where ciliary assembly is defective, chemotaxis towards PDGF-AA is absent, leading to unregulated high speed and uncontrolled directional cell displacement during wound closure, with subsequent defects in wound healing. These data suggest that in coordination with cytoskeletal reorganization, the fibroblast primary cilium functions via ciliary PDGFRα signaling to monitor directional movement during wound healing.

Original languageEnglish (US)
Pages (from-to)279-292
Number of pages14
JournalCellular Physiology and Biochemistry
Volume25
Issue number2-3
DOIs
StatePublished - 2010

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Keywords

  • Cell migration
  • Fibroblasts
  • PDGF-AA
  • PDGFRα
  • Primary cilia
  • Wound healing

ASJC Scopus subject areas

  • Physiology

Cite this

Schneider, L., Cammer, M., Lehman, J., Nielsen, S. K., Guerra, C. F., Veland, I. R., Stock, C., Hoffmann, E. K., Yoder, B. K., Schwab, A., Satir, P., & Christensen, S. T. (2010). Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. Cellular Physiology and Biochemistry, 25(2-3), 279-292. https://doi.org/10.1159/000276562