Inside-Out Radial Migration Facilitates Lineage-Dependent Neocortical Microcircuit Assembly

Neuron. 2015 Jun 3;86(5):1159-66. doi: 10.1016/j.neuron.2015.05.002.

Abstract

Neocortical excitatory neurons migrate radially along the glial fibers of mother radial glial progenitors (RGPs) in a birth-date-dependent inside-out manner. However, the precise functional significance of this well-established orderly neuronal migration remains largely unclear. Here, we show that strong electrical synapses selectively form between RGPs and their newborn progeny and between sister excitatory neurons in ontogenetic radial clones at the embryonic stage. Interestingly, the preferential electrical coupling between sister excitatory neurons, but not that between RGP and newborn progeny, is eliminated in mice lacking REELIN or upon clonal depletion of DISABLED-1, which compromises the inside-out radial neuronal migration pattern in the developing neocortex. Moreover, increased levels of Ephrin-A ligand or receptor that laterally disperse sister excitatory neurons also disrupt preferential electrical coupling between radially aligned sister excitatory neurons. These results suggest that RGP-guided inside-out radial neuronal migration facilitates the initial assembly of lineage-dependent precise columnar microcircuits in the neocortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Lineage
  • Cell Movement / physiology*
  • Chlorocebus aethiops
  • Ependymoglial Cells / physiology*
  • Female
  • Mice
  • Mice, Neurologic Mutants
  • Neocortex / cytology*
  • Neocortex / physiology*
  • Nerve Net / cytology*
  • Nerve Net / physiology*
  • Organ Culture Techniques
  • Pregnancy
  • Reelin Protein