Robo1 regulates the migration and laminar distribution of upper-layer pyramidal neurons of the cerebral cortex

Yuko Gonda, William D. Andrews, Hidenori Tabata, Takashi Namba, John G. Parnavelas, Kazunori Nakajima, Shinichi Kohsaka, Carina Hanashima, Shigeo Uchino

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Abstract

Laminar organization is a key feature of the mammalian cerebral cortex, but the mechanisms by which final positioning and "inside-out" distribution of neurons are determined remain largely unknown. Here, we demonstrate that Robo1, a member of the family of Roundabout receptors, regulates the correct positioning of layers II/III pyramidal neurons in the neocortex. Specifically, we used RNA interference in mice to suppress the expression of Robo1 in a subset of layers II/III neurons, and observed the positions of these cells at distinct developmental stages. In contrast to control neurons that migrated toward the pial surface by P1, Robo1-suppressed neurons exhibited a delay in entering the cortical plate at respective stages. Unexpectedly, after the first postnatal week, these neurons were predominantly located in the upper part of layers II/III, in contrast to control cells that were distributed throughout these layers. Sequential electroporation studies revealed that Robo1-suppressed cells failed to establish the characteristic inside-out neuronal distribution and, instead, they accumulated beneath the marginal zone regardless of their birthdate. These results demonstrate that Robo receptors play a crucial role in neocortical lamination and particularly in the positioning of layers II/III pyramidal neurons.

Original languageEnglish
Pages (from-to)1495-1508
Number of pages14
JournalCerebral Cortex
Volume23
Issue number6
DOIs
Publication statusPublished - 2013 Jun 1

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Keywords

  • Roundabout
  • lamination
  • layers II/III
  • neocortex
  • neuronal positioning

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Gonda, Y., Andrews, W. D., Tabata, H., Namba, T., Parnavelas, J. G., Nakajima, K., Kohsaka, S., Hanashima, C., & Uchino, S. (2013). Robo1 regulates the migration and laminar distribution of upper-layer pyramidal neurons of the cerebral cortex. Cerebral Cortex, 23(6), 1495-1508. https://doi.org/10.1093/cercor/bhs141