Primary cilia are solitary organelles in most quiescent mammalian cell types and coordinate signaling pathways during development and in tissue homeostasis. Defects in assembly or function of primary cilia lead to a plethora of diseases and developmental disorders known as ciliopathies [1]. Objective: We investigated the role of fibroblast primary cilia in coordinating PDGFRa signaling, which is critical in organogenesis and tissue regeneration. Methods and Results: During quiescence, PDGFRa expression is upregulated and the receptor is targeted to the cilium, where it becomes activated by its specific ligand, PDGF-AA, for stimulation of the Akt and the Mek1/2-Erk1/2 pathways to control cell cycle entry and cell migration [2-3]. In cell migration, primary cilia of wt cells orient parallel to one another, perpendicular to a wound in monolayers of quiescent cells. PDGF-AA increases the migration speed and directionality of wt cells, whereas both migration speed and cellular displacement are unaffected by PDGF-AA incubation in Ift88-/- cells, which lack primary cilia. Chemotaxis experiments revealed that wt cells immediately and specifically migrate towards a gradient of PDGF-AA. Ift88-/- cells do not respond to gradients of this ligand. In line with this, in vivo wound healing studies show that Ift88 mutant mice have a reduced rate of wound closure compared to wt mice [3]. We also show that the Na+/H+ exchanger, NHE1, a key player in migratory processes, lies downstream of the ciliary PDGFRa signaling pathway in directional fibroblast migration [4]. Conclusion: The primary cilium functions as a cellular GPS that coordinates PDGFRa signaling to control the speed and direction of cell movement essential in developmental processes and wound healing. [1] Christensen ST et al (2007) Traffic 8:97-109 [2] Schneider L et al (2005) Curr. Biol. 15:1861- 6 [3] Schneider L et al (2010) Comp. Physiol. Biochem. 25:279-92 [4] Schneider L et al (2009) J. Cell Biol. 185:163-76