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Science 311 (5761): 629-632

Copyright © 2006 by the American Association for the Advancement of Science

New Neurons Follow the Flow of Cerebrospinal Fluid in the Adult Brain

Kazunobu Sawamoto,1,4,5* Hynek Wichterle,3 Oscar Gonzalez-Perez,1 Jeremy A. Cholfin,1,2 Masayuki Yamada,6 Nathalie Spassky,1 Noel S. Murcia,7 Jose Manuel Garcia-Verdugo,8 Oscar Marin,9 John L. R. Rubenstein,2 Marc Tessier-Lavigne,10 Hideyuki Okano,5 Arturo Alvarez-Buylla1*

Abstract: In the adult brain, neuroblasts born in the subventricular zone migrate from the walls of the lateral ventricles to the olfactory bulb. How do these cells orient over such a long distance and through complex territories? Here we show that neuroblast migration parallels cerebrospinal fluid (CSF) flow. Beating of ependymal cilia is required for normal CSF flow, concentration gradient formation of CSF guidance molecules, and directional migration of neuroblasts. Results suggest that polarized epithelial cells contribute important vectorial information for guidance of young, migrating neurons.

1 Department of Neurological Surgery and Developmental and Stem Cell Biology Program, University of California San Francisco, San Francisco, CA 94143, USA.
2 Nina Ireland Laboratory of Developmental Neurobiology, University of California San Francisco, San Francisco, CA 94143, USA.
3 Department of Pathology, Columbia University, New York, NY 10032, USA.
4 Bridgestone Laboratory of Developmental and Regenerative Neurobiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
5 Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
6 Central Institute for Experimental Animals, Kawasaki, Kanagawa 216-0001, Japan.
7 Rainbow Center for Childhood Polycystic Kidney Disease, Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106–6003, USA.
8 University of Valencia, Burjassot-46100, Spain.
9 Instituto de Neurosciencias de Alicante of the Consejo Superior de Investigaciones Científicas (CSIC) and University Miguel Hernández, 03550 Sant Joan d'Alacant, Alicante, Spain.
10 Genentech, Inc., South San Francisco, CA 94080–4990, USA.

* To whom correspondence should be addressed. E-mail: sawamoto{at}sc.itc.keio.ac.jp (K.S.); abuylla{at}stemcell.ucsf.edu (A.A.B.)

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