N-syndecan deficiency impairs neural migration in brain.
N-syndecan (syndecan-3) is a transmembrane proteoglycan that is abundantly expressed in the major axonal pathways and in the migratory routes of the developing brain. When ligated by heparin-binding (HB) growth-associated molecule (GAM; pleiotrophin), N-syndecan mediates cortactin-Src kinase-dependent neurite outgrowth. However, the functional role of N-syndecan in brain development remains unexplored. In this study, we show that N-syndecan deficiency perturbs the laminar structure of the cerebral cortex as a result of impaired radial migration. In addition, neural migration in the rostral migratory stream is impaired in the N-syndecan-null mice. We suggest that the migration defect depends on impaired HB-GAM-induced Src kinase activation and haptotactic migration. Furthermore, we show that N-syndecan interacts with EGF receptor (EGFR) at the plasma membrane and is required in EGFR-induced neuronal migration.
Hienola
Anni
A
Neuroscience Center, University of Helsinki, 00014 Helsinki, Finland. anni.hienola@helsinki.fi
Tumova
Sarka
S
Kulesskiy
Evgeny
E
Rauvala
Heikki
H
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000172:deficiency* / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D053670:Syndecan-3; D019061:src-Family Kinases / Q000378:metabolism
D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508302:Sdc3 protein, mouse; D053670:Syndecan-3; C066845:pleiotrophin; D066246:ErbB Receptors; D019061:src-Family Kinases