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

TY - JOUR

T1 - Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts

AU - Schneider, Linda

AU - Cammer, Michael

AU - Lehman, Jonathan

AU - Nielsen, Sonja K

AU - Guerra, Charles F

AU - Veland, Iben R

AU - Stock, Christian

AU - Hoffmann, Else K

AU - Yoder, Bradley K

AU - Schwab, Albrecht

AU - Satir, Peter

AU - Christensen, Søren Tvorup

N1 - Key Words * Fibroblasts * Cell migration * Primary cilia * Wound healing * PDGFRa * PDGF-AA

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

U2 - 10.1159/000276562

DO - 10.1159/000276562

M3 - Journal article

C2 - 20110689

SN - 1015-8987

VL - 25

SP - 279

EP - 292

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

IS - 2-3

ER -