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Directional Cell Migration and Chemotaxis in Wound Healing Response to PDGF-AA Are Coordinated by the Primary Cilium in Fibroblasts

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 PDGFRalpha 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 PDGFRalpha signaling to monitor directional movement during wound healing.

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References
1.
Rogers K, McKee N, Kalnins V . Preferential orientation of centrioles toward the heart in endothelial cells of major blood vessels is reestablished after reversal of a segment. Proc Natl Acad Sci U S A. 1985; 82(10):3272-6. PMC: 397757. DOI: 10.1073/pnas.82.10.3272. View

2.
Lih C, Cohen S, Wang C, Lin-Chao S . The platelet-derived growth factor alpha-receptor is encoded by a growth-arrest-specific (gas) gene. Proc Natl Acad Sci U S A. 1996; 93(10):4617-22. PMC: 39327. DOI: 10.1073/pnas.93.10.4617. View

3.
Tobin J, di Franco M, Eichers E, May-Simera H, Garcia M, Yan J . Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung's disease in Bardet-Biedl syndrome. Proc Natl Acad Sci U S A. 2008; 105(18):6714-9. PMC: 2373327. DOI: 10.1073/pnas.0707057105. View

4.
Gundersen G, Bulinski J . Selective stabilization of microtubules oriented toward the direction of cell migration. Proc Natl Acad Sci U S A. 1988; 85(16):5946-50. PMC: 281882. DOI: 10.1073/pnas.85.16.5946. View

5.
Nobes C, Hall A . Rho GTPases control polarity, protrusion, and adhesion during cell movement. J Cell Biol. 1999; 144(6):1235-44. PMC: 2150589. DOI: 10.1083/jcb.144.6.1235. View