Neurotransmitters and Endothelins Acting on Radial Glial G-Protein-Coupled Receptors Are, Through Proteolytic NRG/ErbB4 Activation, Able to Modify the Migratory Behavior of Neocortical Cells and Mediate Bipolar-to-Multipolar Transition

Lauri Louhivuori, Pauli Turunen, Verna Louhivuori, Ibrahim Al Rayyes, Tommy Nordström, Per Uhlén, Karl Åkerman

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Cell-cell communication plays a central role in the guidance of migrating neurons during the development of the cerebral cortex. Neuregulins (NRGs) are essential mediators for migration and maintenance of the radial glial scaffold. We show, in this study that soluble NRG reduces neuronal motility, causes transition of bipolar cells to multipolar ones, and induces neuronal mitosis. Blocking the NRG receptor, ErbB4, results in reduction of neuron-neuron and neuron-radial glial contacts and causes an increase in neuronal motility. Blocking the radial glial metabotropic glutamate receptor 5 (mGluR5), the nonselective cation channel transient receptor potential 3 (TRPC3), or matrix metalloproteinases (MMPs) results in similar effects as ErbB4 blockade. Soluble NRG counteract the changes in motility pattern. Stimulation of other radial glial G-protein-coupled receptors (GPCRs), such as muscarinic acetylcholine receptors or endothelin receptors counteract all the effect of mGluR5 blockade, but not that of ErbB4, TRPC3, and MMP blockade. The results indicate that neurotransmitters and endothelins acting on radial glial GPCRs are, through proteolytic NRG/ErbB4 activation, able to modify the migratory behavior of neurons.

Original languageEnglish
JournalStem Cells and Development
Volume29
Issue number17
Pages (from-to)1160-1177
Number of pages18
ISSN1547-3287
DOIs
Publication statusPublished - 1 Sep 2020
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1182 Biochemistry, cell and molecular biology
  • calcium
  • migration
  • TRPC
  • mGluR5
  • neuregulin
  • ErbB4
  • METABOTROPIC GLUTAMATE-RECEPTOR
  • EGF RECEPTOR
  • MATRIX METALLOPROTEINASES
  • GABAERGIC INTERNEURONS
  • SUSCEPTIBILITY GENE
  • SUBVENTRICULAR ZONE
  • NEURONAL MIGRATION
  • SIGNALING PATHWAYS
  • NEURAL PRECURSORS
  • NERVOUS-SYSTEM

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