Impaired neuronal positioning and dendritogenesis in the neocortex after cell-autonomous Dab1 suppression.
Reelin and Disabled 1 (Dab1) are essential for positioning migrating neurons in the developing neocortex. Cell-autonomous RNA interference-mediated suppression of Dab1 in migrating neurons destined for layer 2/3 shifted the median position of these cells to deeper positions within the cortex. At the time of migration arrest [embryonic day 20 (E20) to E21], Dab1-suppressed cells were underrepresented in the upper approximately 40 microm of the cortex compared with controls, suggesting that Dab1 is essential for somal translocation through the cell-dense cortical plate. Closer examination of the morphology of Dab1-suppressed neurons at E20 revealed simplified leading processes that are less likely to contact the marginal zone (MZ), in which high levels of Reelin are expressed. Examination of Dab1-suppressed cells 3 d later (postnatal day 2) revealed simplified dendrites that are also less likely to contact the MZ. These data reveal a cell-autonomous role of Dab1 in dendritogenesis in the neocortex and suggest that remodeling of the leading process of a migrating neuron into a nascent dendrite by Reelin/Dab1 signaling plays an important role in cell positioning.
Olson
Eric C
EC
Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Department of Neurology, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kim
Seonhee
S
Walsh
Christopher A
CA
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D003712:Dendrites / Q000502:physiology*; D018274:Electroporation; D005786:Gene Expression Regulation; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D019579:Neocortex / Q000033:anatomy & histology / Q000196:embryology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000091042:Reelin Protein; D015398:Signal Transduction / Q000502:physiology
D017931:DNA Primers; C103773:Dab1 protein, mouse; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse