N-cadherin (Cdh2) Maintains Migration and Postmitotic Survival of Cortical Interneuron Precursors in a Cell-Type-Specific Manner

Cereb Cortex. 2020 Mar 14;30(3):1318-1329. doi: 10.1093/cercor/bhz168.

Abstract

The multiplex role of cadherin-based adhesion complexes during development of pallial excitatory neurons has been thoroughly characterized. In contrast, much less is known about their function during interneuron development. Here, we report that conditional removal of N-cadherin (Cdh2) from postmitotic neuroblasts of the subpallium results in a decreased number of Gad65-GFP-positive interneurons in the adult cortex. We also found that interneuron precursor migration into the pallium was already delayed at E14. Using immunohistochemistry and TUNEL assay in the embryonic subpallium, we excluded decreased mitosis and elevated cell death as possible sources of this defect. Moreover, by analyzing the interneuron composition of the adult somatosensory cortex, we uncovered an unexpected interneuron-type-specific defect caused by Cdh2-loss. This was not due to a fate-switch between interneuron populations or altered target selection during migration. Instead, potentially due to the migration delay, part of the precursors failed to enter the cortical plate and consequently got eliminated at early postnatal stages. In summary, our results indicate that Cdh2-mediated interactions are necessary for migration and survival during the postmitotic phase of interneuron development. Furthermore, we also propose that unlike in pallial glutamatergic cells, Cdh2 is not universal, rather a cell type-specific factor during this process.

Keywords: N-cadherin; cell death; interneuron development; mouse; somatosensory cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / physiology*
  • Cell Movement*
  • Interneurons / physiology*
  • Lateral Ventricles / growth & development
  • Mice
  • Mice, Transgenic
  • Mitosis
  • Neural Stem Cells / physiology*
  • Somatosensory Cortex / growth & development*

Substances

  • Cadherins
  • Cdh2 protein, mouse