Nogo-a regulates neural precursor migration in the embryonic mouse cortex.
Although Nogo-A has been intensively studied for its inhibitory effect on axonal regeneration in the adult central nervous system, little is known about its function during brain development. In the embryonic mouse cortex, Nogo-A is expressed by radial precursor/glial cells and by tangentially migrating as well as postmigratory neurons. We studied radially migrating neuroblasts in wild-type and Nogo-A knockout (KO) mouse embryos. In vitro analysis showed that Nogo-A and its receptor components NgR, Lingo-1, TROY, and p75 are expressed in cells emigrating from embryonic forebrain-derived neurospheres. Live imaging revealed an increased cell motility when Nogo-A was knocked out or blocked with antibodies. Antibodies blocking NgR or Lingo-1 showed the same motility-enhancing effect supporting a direct role of surface Nogo-A on migration. Bromodeoxyuridine (BrdU) labeling of embryonic day (E)15.5 embryos demonstrated that Nogo-A influences the radial migration of neuronal precursors. At E17.5, the normal transient accumulation of radially migrating precursors within the subventricular zone was not detectable in the Nogo-A KO mouse cortex. At E19, migration to the upper cortical layers was disturbed. These findings suggest that Nogo-A and its receptor complex play a role in the interplay of adhesive and repulsive cell interactions in radial migration during cortical development.
Mathis
Carole
C
Brain Research Institute, University of Zurich and Department of Biology, ETH Zurich, 8057 Zurich, Switzerland.
Schröter
Aileen
A
Thallmair
Michaela
M
Schwab
Martin E
ME
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D000089622:Doublecortin Domain Proteins; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009185:Myelin Proteins / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D000070798:Nogo Proteins; D018000:Receptors, Peptide / Q000378:metabolism; D018709:Statistics, Nonparametric; D014404:Tubulin / Q000378:metabolism
D000089622:Doublecortin Domain Proteins; C523678:LINGO1 protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000070798:Nogo Proteins; D018000:Receptors, Peptide; C000603201:Rtn4 protein, mouse; D014404:Tubulin; C462941:beta3 tubulin, mouse; D001973:Bromodeoxyuridine