Molecular mechanisms controlling the migration of striatal interneurons

J Neurosci. 2015 Jun 10;35(23):8718-29. doi: 10.1523/JNEUROSCI.4317-14.2015.

Abstract

In the developing telencephalon, the medial ganglionic eminence (MGE) generates many cortical and virtually all striatal interneurons. While the molecular mechanisms controlling the migration of interneurons to the cortex have been extensively studied, very little is known about the nature of the signals that guide interneurons to the striatum. Here we report that the allocation of MGE-derived interneurons in the developing striatum of the mouse relies on a combination of chemoattractive and chemorepulsive activities. Specifically, interneurons migrate toward the striatum in response to Nrg1/ErbB4 chemoattraction, and avoid migrating into the adjacent cortical territories by a repulsive activity mediated by EphB/ephrinB signaling. Our results also suggest that the responsiveness of MGE-derived striatal interneurons to these cues is at least in part controlled by the postmitotic activity of the transcription factor Nkx2-1. This study therefore reveals parallel mechanisms for the migration of MGE-derived interneurons to the striatum and the cerebral cortex.

Keywords: Eph; ErbB4; GABAergic; interneuron; migration; striatum.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Cell Movement / genetics*
  • Cerebellar Cortex / cytology
  • Corpus Striatum / cytology*
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental
  • Humans
  • In Vitro Techniques
  • Interneurons / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mutation / genetics
  • Neural Pathways / physiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Organ Culture Techniques
  • Receptor, EphB1 / genetics
  • Receptor, EphB1 / metabolism
  • Receptor, EphB3 / genetics
  • Receptor, EphB3 / metabolism
  • Receptor, ErbB-4 / genetics
  • Receptor, ErbB-4 / metabolism
  • Signal Transduction
  • Telencephalon / cytology
  • Telencephalon / embryology
  • Thyroid Nuclear Factor 1
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Nkx2-1 protein, mouse
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • ERBB4 protein, human
  • Receptor, EphB1
  • Receptor, EphB3
  • Receptor, ErbB-4