Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts.
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.
Schneider
Linda
L
Department of Biology, Section of Cell and Developmental Biology, The August Krogh Building, University of Copenhagen, DK-2100 Copenhagen OE, Denmark.
Cammer
Michael
M
Lehman
Jonathan
J
Nielsen
Sonja K
SK
Guerra
Charles F
CF
Veland
Iben R
IR
Stock
Christian
C
Hoffmann
Else K
EK
Yoder
Bradley K
BK
Schwab
Albrecht
A
Satir
Peter
P
Christensen
Søren T
ST
D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D002923:Cilia / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D010982:Platelet-Derived Growth Factor; C490898:Tg737Rpw protein, mouse; D025521:Tumor Suppressor Proteins; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha