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Nodal Cilia Dynamics and the Specification of the Left/Right Axis in Early Vertebrate Embryo Development

Javier Buceta ^*, Marta Ibañes , Diego Rasskin-Gutman , Yasushi Okada , Nobutaka Hirokawa  and Juan Carlos Izpisúa-Belmonte 

^* Centre de Recerca en Química Teòrica (CeRQT), Parc Científic de Barcelona, Campus Diagonal-Universitat de Barcelona, Edifici Modular, Barcelona, Spain; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California; and Department of Cell Biology & Anatomy, University of Tokyo, Graduate School of Medicine, Tokyo, Japan

Correspondence: Address reprint requests and inquiries to J. Buceta, E-mail: jbuceta{at}pcb.ub.es or J. C. Izpisúa-Belmonte, E-mail: belmonte{at}salk.edu.

Nodal cilia dynamics is a key factor for left/right axis determination in mouse embryos through the induction of a leftward fluid flow. So far it has not been clearly established how such dynamics is able to induce the asymmetric leftward flow within the node. Herein we propose that an asymmetric two-phase nonplanar beating cilia dynamics that involves the bending of the ciliar axoneme is responsible for the leftward fluid flow. We support our proposal with a host of hydrodynamic arguments, in silico experiments and in vivo video microscopy data in wild-type embryos and inv mutants. Our phenomenological modeling approach underscores how the asymmetry and speed of the flow depends on different relevant parameters. In addition, we discuss how the combination of internal and external mechanisms might cause the two-phase beating cilia dynamics.

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