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.
Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Department of Neurology, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.
Eric C
EC
Olson
Seonhee
S
Kim
Christopher A
CA
Walsh
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