Research Article

Cilia at the Node of Mouse Embryos Sense Fluid Flow for Left-Right Determination via Pkd2

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Science  12 Oct 2012:
Vol. 338, Issue 6104, pp. 226-231
DOI: 10.1126/science.1222538

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Distinguishing Right from Left

In most vertebrates during embryonic development, rotational movement of the cilia within a structure in the embryo, known as the node, generates unidirectional flow required for future left-right asymmetry of the internal organs. The flow may transport a determinant molecule or provide mechanical force. However, it is not clear how the flow is sensed. Yoshiba et al. (p. 226, published online 13 September; see the Perspective by Norris and Grimes) show that nodal flow in mouse embryos is sensed by the cilia of perinodal cells located at the edge of the node, in a manner dependent on Pkd2, a Ca2+-permeable cation channel that has been implicated in polycystic kidney disease in humans.

Abstract

Unidirectional fluid flow plays an essential role in the breaking of left-right (L-R) symmetry in mouse embryos, but it has remained unclear how the flow is sensed by the embryo. We report that the Ca2+ channel Polycystin-2 (Pkd2) is required specifically in the perinodal crown cells for sensing the nodal flow. Examination of mutant forms of Pkd2 shows that the ciliary localization of Pkd2 is essential for correct L-R patterning. Whereas Kif3a mutant embryos, which lack all cilia, failed to respond to an artificial flow, restoration of primary cilia in crown cells rescued the response to the flow. Our results thus suggest that nodal flow is sensed in a manner dependent on Pkd2 by the cilia of crown cells located at the edge of the node.

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