title: OCAM regulates embryonic spinal cord stem cell proliferation by modulating ErbB2 receptor.
abstract: 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.
authors: Department of Neurosurgery, College of Medicine, University of Florida Gainesville, Gainesville, Florida, United States of America.
authors: Loïc
authors: L
authors: Deleyrolle
authors: INSERM U1051, Institute for Neuroscience, Hôpital Saint Eloi, Montpellier, France.
authors: Jean-Charles
authors: JC
authors: Sabourin
authors: INSERM U1051, Institute for Neuroscience, Hôpital Saint Eloi, Montpellier, France.
authors: Bernard
authors: B
authors: Rothhut
authors: RIKEN Brain Science Institute, Saitama, Japan.
authors: Hiroko
authors: H
authors: Fujita
authors: INSERM U1051, Institute for Neuroscience, Hôpital Saint Eloi, Montpellier, France.
authors: Pierre-Olivier
authors: PO
authors: Guichet
authors: INSERM U1051, Institute for Neuroscience, Hôpital Saint Eloi, Montpellier, France.
authors: Marisa
authors: M
authors: Teigell
authors: INSERM U1051, Institute for Neuroscience, Hôpital Saint Eloi, Montpellier, France.
authors: Chantal
authors: C
authors: Ripoll
authors: INSERM U661, Department of Endocrinology, Institute of Functional Genomics, Montpellier, France; University of Montpellier 2, Montpellier, France.
authors: Norbert
authors: N
authors: Chauvet
authors: INSERM U1051, Institute for Neuroscience, Hôpital Saint Eloi, Montpellier, France.
authors: Florence
authors: F
authors: Perrin
authors: INSERM U1051, Institute for Neuroscience, Hôpital Saint Eloi, Montpellier, France.
authors: Daria
authors: D
authors: Mamaeva
authors: Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Tetsuo
authors: T
authors: Noda
authors: Department of Physiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Kensaku
authors: K
authors: Mori
authors: RIKEN Brain Science Institute, Saitama, Japan.
authors: Yoshihiro
authors: Y
authors: Yoshihara
authors: INSERM U1051, Institute for Neuroscience, Hôpital Saint Eloi, Montpellier, France; University of Montpellier 2, Montpellier, France.
authors: Jean-Philippe
authors: JP
authors: Hugnot
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism*
chemical_list: D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C108768:Ncam2 protein, mouse; C524056:Erbb2 protein, mouse