Overlapping functions of the cell adhesion molecules Nr-CAM and L1 in cerebellar granule cell development.
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.
Sakurai
T
T
W.M. Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
Lustig
M
M
Babiarz
J
J
Furley
A J
AJ
Tait
S
S
Brophy
P J
PJ
Brown
S A
SA
Brown
L Y
LY
Mason
C A
CA
Grumet
M
M
D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000187:drug effects / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D058966:Contactins; D005260:Female; D039841:Leukocyte L1 Antigen Complex; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D019006:Neural Cell Adhesion Molecules / Q000494:pharmacology* / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D017027:Protein Tyrosine Phosphatases / Q000494:pharmacology; D011689:Purkinje Cells / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C491151:Nrcam protein, mouse; D017027:Protein Tyrosine Phosphatases; C516896:Ptprz1 protein, mouse; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5