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J Neurosci. 2011 Jun 22;31(25):9426-39. doi: 10.1523/JNEUROSCI.0650-11.2011.

The outermost region of the developing cortical plate is crucial for both the switch of the radial migration mode and the Dab1-dependent "inside-out" lamination in the neocortex.

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Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan.


Mammalian neocortex has a laminated structure that develops in a birth-date-dependent "inside-out" pattern. This layered structure is established by neuronal migration with sequential changes of the migratory mode regulated by several signaling cascades, including the Reelin-Disabled homolog 1 (Dab1) pathway. Although the importance of "locomotion," the major migratory mode, has been well established, the physiological significance of the mode change from locomotion to "terminal translocation," the final migratory mode, is unknown. In this study, we found that the outermost region of the mouse cortical plate has several histologically distinct features and named this region the primitive cortical zone (PCZ). Time-lapse analyses revealed that "locomoting" neurons paused transiently just beneath the PCZ before migrating into it by "terminal translocation." Furthermore, whereas Dab1-knockdown (KD) neurons could reach beneath the PCZ, they failed to enter the PCZ, suggesting that the Dab1-dependent terminal translocation is necessary for entry of the neurons into the PCZ. Importantly, sequential in utero electroporation experiments directly revealed that failure of the Dab1-dependent terminal translocation resulted in disruption of the inside-out alignment within the PCZ and that this disrupted pattern was still preserved in the mature cortex. Conversely, Dab1-KD locomoting neurons could pass by both wild-type and Dab1-KD predecessors beneath the PCZ. Our data indicate that the PCZ is a unique environment, passage of neurons through which involves molecularly and behaviorally different migratory mechanisms, and that the migratory mode change from locomotion to terminal translocation just beneath the PCZ is critical for the Dab1-dependent inside-out lamination in the mature cortex.

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