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A correction to this article has been published: J. Cell Biol. 155 (2) 311
Published 17 September 2001. doi:10.1083/jcb.200104122
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© The Rockefeller University Press, 0021-9525/2001/9/1259 $5.00
The Journal of Cell Biology, Volume 154, Number 6, September 17, 2001 1259-1274

Article

Overlapping functions of the cell adhesion molecules Nr-CAM and L1 in cerebellar granule cell development



Takeshi Sakurai1, Marc Lustig2, Joanne Babiarz1, Andrew J.W. Furley3, Steven Tait4, Peter J. Brophy4, Stephen A. Brown5, Lucia Y. Brown5, Carol A. Mason6 and Martin Grumet1

1 W.M. Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854
2 Department of Pharmacology, New York University Medical Center, New York, NY 10016
3 Centre for Developmental Genetics, University of Sheffield, Sheffield S10 2TN, UK
4 Department of Preclinical Veterinary Sciences, University of Edinburgh, Edinburgh EH8 9YL, UK
5 Department of Obstetrics and Gynocology, Anatomy and Cell Biology, and Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, New York, NY 10032
6 Department of Pathology, Anatomy and Cell Biology, and Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, New York, NY 10032

Address correspondence to Martin Grumet, W.M. Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, 604 Allison Rd., Piscataway, NJ 08854-8082. Tel.: (732) 445-6577. Fax: (732) 445-2063. E-mail: mgrumet{at}rci.rutgers.edu

The structurally related cell adhesion molecules L1 and Nr-CAM have overlapping expression patterns in cerebellar granule cells. Here we analyzed their involvement in granule cell development using mutant mice. Nr-CAM–deficient cerebellar granule cells failed to extend neurites in vitro on contactin, a known ligand for Nr-CAM expressed in the cerebellum, confirming that these mice are functionally null for Nr-CAM. In vivo, Nr-CAM–null cerebella did not exhibit obvious histological defects, although a mild size reduction of several lobes was observed, most notably lobes IV and V in the vermis. Mice deficient for both L1 and Nr-CAM exhibited severe cerebellar folial defects and a reduction in the thickness of the inner granule cell layer. Additionally, anti-L1 antibodies specifically disrupted survival and maintenance of Nr-CAM–deficient granule cells in cerebellar cultures treated with antibodies. The combined results indicate that Nr-CAM and L1 play a role in cerebellar granule cell development, and suggest that closely related molecules in the L1 family have overlapping functions.

Key Words: cerebellum; Nr-CAM; L1; cell adhesion molecule; development


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