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


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(1) cannabinoid receptor (CB(1)R) null and pyramidal cell-specific conditional mutant (CB(1)R(f/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.

SUBMITTER: Mulder J 

PROVIDER: S-EPMC2438381 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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

Mulder Jan J   Aguado Tania T   Keimpema Erik E   Barabás Klaudia K   Ballester Rosado Carlos J CJ   Nguyen Laurent L   Monory Krisztina K   Marsicano Giovanni G   Di Marzo Vincenzo V   Hurd Yasmin L YL   Guillemot Francois F   Mackie Ken K   Lutz Beat B   Guzmán Manuel M   Lu Hui-Chen HC   Galve-Roperh Ismael I   Harkany Tibor T  

Proceedings of the National Academy of Sciences of the United States of America 20080618 25


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  ...[more]

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