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The Journal of Neuroscience, February 8, 2006, 26(6):1767-1775; doi:10.1523/JNEUROSCI.3000-05.2006

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Development/Plasticity/Repair
Impaired Neuronal Positioning and Dendritogenesis in the Neocortex after Cell-Autonomous Dab1 Suppression

Eric C. Olson, Seonhee Kim, and Christopher A. Walsh

Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Department of Neurology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115

Correspondence should be addressed to Dr. Christopher A. Walsh, Howard Hughes Medical Institute, Department of Neurology, Beth Israel Deaconess Medical Center, New Research Building, 77 Avenue Louis Pasteur, Room 0233, Boston, MA 02115. Email: cwalsh{at}bidmc.harvard.edu

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 40 µm 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.

Key words: Reelin; lamination; Dab1; migration; branching; dendrite

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Received July 20, 2005; revised Dec. 22, 2005; accepted Dec. 29, 2005.

Correspondence should be addressed to Dr. Christopher A. Walsh, Howard Hughes Medical Institute, Department of Neurology, Beth Israel Deaconess Medical Center, New Research Building, 77 Avenue Louis Pasteur, Room 0233, Boston, MA 02115. Email: cwalsh{at}bidmc.harvard.edu

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