Journal Article

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

Yoshiba, Satoko, Dworniczak, Bernd, Kuo, Ivana Y., Belo, Jose Antonio, Hamada, Hiroshi, Nonaka, Shigenori, Shiratori, Hidetaka, Nakai, Junichi, Sasaki, Hiroshi, Ehrlich, Barbara E., Asai, Yasuko, Sasaki, Genta, Pennekamp, Petra, Kawasumi, Aiko, Shinohara, Kyosuke

2012

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Animals / Asymmetry / Biological and medical sciences / Body Fluids - physiology / Body Patterning / calcium / Calcium - metabolism / cations / Cellular biology / Channel / Channels / Cilia / Cilia - metabolism / Cilia - physiology / Embryo, Mammalian - anatomy & histology / Embryo, Mammalian - cytology / Embryo, Mammalian - physiology / embryogenesis / Embryology: invertebrates and vertebrates. Teratology / Embryonic growth stage / Embryos / Emerging technology / Endothelial cells / Epithelial cells / Expression / Fluid dynamics / Fluid flow / Fundamental and applied biological sciences. Psychology / Gene Expression Regulation, Developmental / Human / humans / Intercellular Signaling Peptides and Proteins - metabolism / Kidney diseases / Kif3A / Kinesins - genetics / Lacking / Left-Right Determination Factors - genetics / Left-Right Determination Factors - metabolism / LLC PK1 cells / Mechanical forces / Mice / Mice, Mutant Strains / Mutagenesis / Mutation / Organizers, Embryonic - cytology / Organizers, Embryonic - physiology / Organogenesis. Fetal development / Organogenesis. Physiological fonctions / Organs / Polycystic kidney disease / polycystic kidney diseases / Protein / Release / Signal Transduction / Symmetry / Transgenes / Transgenic animals / TRPP Cation Channels - genetics / TRPP Cation Channels - metabolism / Vertebrates