Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 25, Pages 8760-8765Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0803545105
Keywords
excitation; glutamate; layer patterning; neocortex; neurogenesis
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Funding
- MRC [MC_U117570528] Funding Source: UKRI
- Medical Research Council [MC_U117570528] Funding Source: researchfish
- Medical Research Council [MC_U117570528] Funding Source: Medline
- NIDA NIH HHS [DA15916, R01 DA011322, R01DA023214, DA11322, R01 DA023214, P01 DA015916, K05 DA021696, DA21696] Funding Source: Medline
- NIEHS NIH HHS [ES07332, T32 ES007332] Funding Source: Medline
- NINDS NIH HHS [R01 NS048884, NS048884] Funding Source: Medline
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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.
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