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

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.

Voltage-Gated Na+Channel β1 Subunit-Mediated Neurite Outgrowth Requires Fyn Kinase and Contributes to Postnatal CNS DevelopmentIn Vivo

“…Similar to the present data, Cntn null mice display misorientation of the parallel fibers with a slight reduction in their compaction within fascicles (Berglund et al, 1999). In contrast, in L1cam or Nrcam null mice, there was a reduction in the thickness of both the EGL and the IGL, without any alteration in the pattern of TAG-1 expression, suggesting that, unlike ␤1, these adhesion molecules may be important for CGN proliferation and/or cell survival, in addition to migration (Sakurai et al, 2001).…”

L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth

“…Other L1-CAMs might contribute to radial migration of neurons in different brain regions. In this regard it is interesting that L1 and NrCAM double knockout mice exhibit a cerebellar phenotype consistent with impaired migration [15].…”

Ankyrin-Dependent and -Independent Mechanisms Orchestrate Axonal Compartmentalization of L1 Family Members Neurofascin and L1/Neuron–Glia Cell Adhesion Molecule

“…The idea that NF first travels to the axon generally from the secretory pathway is also suggested by the transient broad axonal localization of NF in very young stage 3 neurons (phase IS1). An early axonal targeting might account for the proposed roles of NF and NrCAM in axon outgrowth and pathfinding in the chick and mouse visual system (Sakurai et al, 2001;Pruss et al, 2004Pruss et al, , 2006Zelina et al, 2005;Williams et al, 2006). After axon outgrowth and synaptogenesis are complete, secretory IS targeting might develop as a mature mechanism to efficiently enrich IS components at the IS later on.…”