Correct setup of the substantia nigra requires Reelin-mediated fast, laterally-directed migration of dopaminergic neurons

Elife. 2019 Jan 28;8:e41623. doi: 10.7554/eLife.41623.

Abstract

Midbrain dopaminergic (mDA) neurons migrate to form the laterally-located substantia nigra pars compacta (SN) and medially-located ventral tegmental area (VTA), but little is known about the underlying cellular and molecular processes. Here we visualize the dynamic cell morphologies of tangentially migrating SN-mDA neurons in 3D and identify two distinct migration modes. Slow migration is the default mode in SN-mDA neurons, while fast, laterally-directed migration occurs infrequently and is strongly associated with bipolar cell morphology. Tangential migration of SN-mDA neurons is altered in absence of Reelin signaling, but it is unclear whether Reelin acts directly on migrating SN-mDA neurons and how it affects their cell morphology and migratory behavior. By specifically inactivating Reelin signaling in mDA neurons we demonstrate its direct role in SN-mDA tangential migration. Reelin promotes laterally-biased movements in mDA neurons during their slow migration mode, stabilizes leading process morphology and increases the probability of fast, laterally-directed migration.

Keywords: Dab1; cell morphology; cell tracking; developmental biology; dopaminergic system; mouse; neuroscience; organotypic slice cultures; time-lapse imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Movement*
  • Cell Shape
  • Dopaminergic Neurons / cytology*
  • Dopaminergic Neurons / metabolism
  • Extracellular Matrix Proteins / metabolism*
  • Mesencephalon / cytology
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Phosphorylation
  • Serine Endopeptidases / metabolism*
  • Signal Transduction
  • Substantia Nigra / cytology*
  • Ventral Tegmental Area / cytology

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Serine Endopeptidases
  • reelin protein