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

Jan Mulder1, Tania Aguado, Erik Keimpema

  • 1Department of Neuroscience, Retzius väg 8, and Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Scheeles väg 1, Karolinska Institutet, 17177 Stockholm, Sweden.

Proceedings of the National Academy of Sciences of the United States of America
|June 20, 2008
PubMed
Summary

Endocannabinoids (eCBs) are crucial for pyramidal cell development in the brain. This study reveals eCB signaling controls progenitor proliferation, migration, and long-range axon growth during corticogenesis.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Endocannabinoids (eCBs) are known axon guidance cues for local interneurons.
  • The role of eCBs in pyramidal cell development, including specification and long-range axon formation, remains largely unknown.

Purpose of the Study:

  • To investigate the function of eCB signaling in pyramidal cell development during mouse corticogenesis.
  • To determine the impact of eCBs on pyramidal cell progenitor proliferation, migration, and axon elongation.

Main Methods:

  • Utilized CB(1) cannabinoid receptor (CB(1)R) null and conditional mutant mice (CB(1)R(f/f,NEX-Cre)).
  • Employed in utero pharmacological blockade of CB(1)Rs.
  • Analyzed neuronal progenitor proliferation, radial migration, and axon fasciculation.

Main Results:

  • eCB signaling is active in the developing mouse telencephalon from embryonic day 12.
  • eCBs regulate the proliferation of pyramidal cell progenitors and the radial migration of immature pyramidal cells.
  • Disruption of eCB signaling impairs axon elongation, fasciculation, and pathfinding of pyramidal cell axons.

Conclusions:

  • Endocannabinoids are fundamental developmental cues controlling pyramidal cell development.
  • eCB signaling is essential for both early progenitor/migration events and later axon guidance during corticogenesis.