TAG-1 Multifunctionality Coordinates Neuronal Migration, Axon Guidance, and Fasciculation

Cell Rep. 2020 Jan 28;30(4):1164-1177.e7. doi: 10.1016/j.celrep.2019.12.085.

Abstract

Neuronal migration, axon fasciculation, and axon guidance need to be closely coordinated for neural circuit assembly. Spinal motor neurons (MNs) face unique challenges during development because their cell bodies reside within the central nervous system (CNS) and their axons project to various targets in the body periphery. The molecular mechanisms that contain MN somata within the spinal cord while allowing their axons to exit the CNS and navigate to their final destinations remain incompletely understood. We find that the MN cell surface protein TAG-1 anchors MN cell bodies in the spinal cord to prevent their emigration, mediates motor axon fasciculation during CNS exit, and guides motor axons past dorsal root ganglia. TAG-1 executes these varied functions in MN development independently of one another. Our results identify TAG-1 as a key multifunctional regulator of MN wiring that coordinates neuronal migration, axon fasciculation, and axon guidance.

Keywords: TAG-1; adhesion; axon guidance; development; fasciculation; motor neurons; neuronal migration; spinal cord.

MeSH terms

  • Animals
  • Axon Guidance / genetics*
  • Axon Guidance / physiology
  • Axons / metabolism
  • COS Cells
  • Cell Line
  • Cell Movement / genetics*
  • Chlorocebus aethiops
  • Contactin 2 / genetics
  • Contactin 2 / metabolism*
  • Fasciculation / genetics
  • Fasciculation / metabolism*
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Neurons / metabolism*
  • Neurogenesis / genetics*
  • Signal Transduction / genetics
  • Spinal Cord / metabolism

Substances

  • Cntn2 protein, mouse
  • Contactin 2