Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning

Jan Mulder, Tania Aguado, Erik Keimpema, Klaudia Barabas, Carlos J. Ballester Rosado, Laurent Nguyen, Krisztina Monory, Giovanni Marsicano, Vincenzo Di Marzo, Yasmin L. Hurd, Francois Guillemot, Ken Mackie, Beat Lutz, Manuel Guzman, Hui-Chen Lu, Ismael Galve-Roperh, Tibor Harkany

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175 Citations (Scopus)

Abstract

Endocannabinoids (eCBs) have recently been identified as axon guidance cues shaping the connectivity of local GABAergic interneurons in the developing cerebrum. However, eCB functions during pyramidal cell specification and establishment of long-range axonal connections are unknown. Here, we show that eCB signaling is operational in subcortical proliferative zones from embryonic day 12 in the mouse telencephalon and controls the proliferation of pyramidal cell progenitors and radial migration of immature pyramidal cells. When layer patterning is accomplished, developing pyramidal cells rely on eCB signaling to initiate the elongation and fasciculation of their long-range axons. Accordingly, CB, cannabinoid receptor (CB1R) null and pyramidal cell-specific conditional mutant (CB1Rf/f,NEX-Cre) mice develop deficits in neuronal progenitor proliferation and axon fasciculation. Likewise, axonal pathfinding becomes impaired after in utero pharmacological blockade of CB(1)Rs. Overall, eCBs are fundamental developmental cues controlling pyramidal cell development during corticogenesis.

Original languageEnglish
Pages (from-to)8760-8765
Number of pages6
JournalPNAS
Volume105
Issue number25
DOIs
Publication statusPublished - 2008

Keywords

  • excitation
  • glutamate
  • layer patterning
  • neocortex
  • neurogenesis
  • CB1cannabinoid receptor
  • principal neurons
  • progenitor cells
  • brain
  • hippocampus
  • migration
  • system
  • mice
  • differentiation

Cite this

Mulder, J., Aguado, T., Keimpema, E., Barabas, K., Rosado, C. J. B., Nguyen, L., Monory, K., Marsicano, G., Di Marzo, V., Hurd, Y. L., Guillemot, F., Mackie, K., Lutz, B., Guzman, M., Lu, H-C., Galve-Roperh, I., & Harkany, T. (2008). Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning. PNAS, 105(25), 8760-8765. https://doi.org/10.1073/pnas.0803545105