Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning.
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.
Mulder
Jan
J
Department of Neuroscience, Retzius väg 8, and Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Scheeles väg 1, Karolinska Institutet, 17177 Stockholm, Sweden.
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
D000818:Animals; D001369:Axons / Q000378:metabolism*; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002454:Cell Differentiation; D063388:Endocannabinoids; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism*; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043882:Receptors, Cannabinoid