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

Takeshi Sakurai, Marc Lustig, Joanne Babiarz, Andrew J.W. Furley, Steven Tait, Peter J. Brophy, Stephen A. Brown, Lucia Y. Brown, Carol A. Mason, Martin Grumet

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1259-1273
Number of pages15
JournalJournal of Cell Biology
Volume154
Issue number6
DOIs
StatePublished - Sep 17 2001

All Science Journal Classification (ASJC) codes

  • Cell Biology

Keywords

  • Cell adhesion molecule
  • Cerebellum
  • Development
  • L1
  • Nr-CAM

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