Sci. Signal., 6 April 2010
Cilia Determining the Flow
John F. Foley
Science Signaling, AAAS, Washington, DC 20005, USA
Cilia are plasma membrane projections that regulate the flow of extracellular fluid, which is critical in processes as diverse as the directional movement of mucus in the respiratory tract and the formation of morphogen gradients during development. These functions depend on the coordinated orientation of cilia so that they beat in the same direction; however, the cues that regulate ciliary orientation are unclear. Some studies suggest that planar cell polarity (PCP) signaling, which regulates the apical orientation of cells during development, is required for the proper positioning of cilia, whereas other studies have implicated the effects of fluid flow on cilia (see commentary by Marshall). Two groups now show that both the PCP pathway and flow are required for ciliary orientation. Guirao et al. studied ciliary orientation in ependymal cells in the ventricles of mouse brains. During the development of these cells, the basal bodies of cilia docked at the apical surface in a random orientation. Over time, however, the resulting cilia oriented themselves to align with the direction of cerebrospinal fluid flow. In vitro studies showed that the flow-dependent realignment of cilia required the PCP signaling component Van Gogh-like 2 (Vangl2), which is found along the cilium and at the basal body. Borovina et al. studied zebrafish embryos that lacked Vangl2 and found that the tilt angle and the asymmetric localization of cilia in the Kuppfers vesicle were impaired. Together, these studies suggest that the integration of hydrodynamic forces and PCP is required for proper ciliary orientation. The initial force exerted by flow acts as a long-range signal that triggers the self-organization of cilia through a mechanism that depends on PCP signaling.
B. Guirao, A. Meunier, S. Mortaud, A. Aguilar, J.-M. Corsi, L. Strehl, Y. Hirota, A. Desoeuvre, C. Boutin, Y.-G. Han, Z. Mirzadeh, H. Cremer, M. Montcouquiol, K. Sawamoto, N. Spassky, Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia. Nat. Cell Biol. 12, 341–350 (2010). [PubMed]
A. Borovina, S. Superina, D. Voskas, B. Ciruna, Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia. Nat. Cell Biol. 12, 407–412 (2010). [PubMed]
W. F. Marshall, Cilia self-organize in response to planar cell polarity and flow. Nat. Cell Biol. 12, 314–315 (2010). [PubMed]
Citation: J. F. Foley, Determining the Flow. Sci. Signal. 3, ec102 (2010).
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