4.8 Article

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

期刊

NEURON
卷 86, 期 5, 页码 1159-1166

出版社

CELL PRESS
DOI: 10.1016/j.neuron.2015.05.002

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资金

  1. Simons Foundation
  2. National Institutes of Health [R01DA024681, R01MH101382]
  3. Natural Science Foundation of China [31228012]
  4. Tri-Institutional Stem Cell Initiative STARR Stem Cell Fellowship

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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.

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