Send to

Choose Destination
PLoS One. 2015 Apr 13;10(4):e0122337. doi: 10.1371/journal.pone.0122337. eCollection 2015.

OCAM regulates embryonic spinal cord stem cell proliferation by modulating ErbB2 receptor.

Author information

Department of Neurosurgery, College of Medicine, University of Florida Gainesville, Gainesville, Florida, United States of America.
INSERM U1051, Institute for Neuroscience, Hôpital Saint Eloi, Montpellier, France.
RIKEN Brain Science Institute, Saitama, Japan.
INSERM U661, Department of Endocrinology, Institute of Functional Genomics, Montpellier, France; University of Montpellier 2, Montpellier, France.
Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Physiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
INSERM U1051, Institute for Neuroscience, Hôpital Saint Eloi, Montpellier, France; University of Montpellier 2, Montpellier, France.


The proliferation and differentiation of neural stem cells are tightly controlled by intrinsic and extrinsic cues. Cell adhesion molecules are increasingly recognized as regulators of these processes. Here we report the expression of the olfactory cell adhesion molecule (OCAM/NCAM2/RNCAM) during mouse spinal cord development and in neural stem cells cultured as neurospheres. OCAM is also weakly expressed in the dormant adult stem cell niche around the central canal and is overexpressed after spinal cord injury. Both transmembrane (TM) and glycosylphosphatidylinositol (GPI)-linked isoforms are present in neurospheres. Electron microscopy and internalisation experiments revealed a dynamic trafficking of OCAM between the membrane and intracellular compartments. After differentiation, OCAM remains in neurons and oligodendrocytes whereas no expression is detected in astrocytes. Using OCAM knockout (KO) mice, we found that mutant spinal cord stem cells showed an increased proliferation and self-renewal rates although no effect on differentiation was observed. This effect was reversed by lentivirus-mediated re-introduction of OCAM. Mechanistically, we identified the ErbB2/Neu/HER2 protein as being implicated in the enhanced proliferation of mutant cells. ErbB2 protein expression and phosphorylation level were significantly increased in KO cells whereas no difference was observed at the mRNA level. Overexpression of ErbB2 in wild-type and mutant cells also increased their growth while reintroduction of OCAM in mutant cells reduced the level of phosphorylated ErbB2. These results indicate that OCAM exerts a posttranscriptional control on the ErbB2 signalling in spinal cord stem cells. This study adds further support for considering cell adhesion molecules as regulators of the ErbB signalling.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center