RT Journal Article
T1 Endocannabinoid signalling in stem cells and cerebral organoids drives differentiation to deep layer projection neurons via CB1 receptors
A1 Paraíso Luna, Juan
A1 Aguareles Gorines, José
A1 Martín Herranz, Ricardo
A1 Ayo-Martín, Ane
A1 Simón-Sánchez, Samuel
A1 García Rincón, Daniel
A1 Costas Insúa, Carlos
A1 García-Taboada, Elena
A1 de salas-quiroga, adan
A1 Díaz-Alonso, Javier
A1 Liste, Isabel
A1 Sánchez-Prieto Borja, José
A1 Cappello, Silvia
A1 Guzmán Pastor, Manuel
A1 Galve Roperh, Ismael
AB The endocannabinoid (eCB) system, via the cannabinoid CB1 receptor, regulates neurodevelopment by controlling neural progenitor proliferation and neurogenesis. CB1 receptor signalling in vivo drives corticofugal deep layer projection neuron development through the regulation of BCL11B and SATB2 transcription factors. Here, we investigated the role of eCB signalling in mouse pluripotent embryonic stem cell-derived neuronal differentiation. Characterization of the eCB system revealed increased expression of eCB-metabolizing enzymes, eCB ligands and CB1 receptors during neuronal differentiation. CB1 receptor knockdown inhibited neuronal differentiation of deep layer neurons and increased upper layer neuron generation, and this phenotype was rescued by CB1 re-expression. Pharmacological regulation with CB1 receptor agonists or elevation of eCB tone with a monoacylglycerol lipase inhibitor promoted neuronal differentiation of deep layer neurons at the expense of upper layer neurons. Patch-clamp analyses revealed that enhancing cannabinoid signalling facilitated neuronal differentiation and functionality. Noteworthy, incubation with CB1 receptor agonists during human iPSC-derived cerebral organoid formation also promoted the expansion of BCL11B+ neurons. These findings unveil a cell-autonomous role of eCB signalling that, via the CB1 receptor, promotes mouse and human deep layer cortical neuron development.
PB The company of biologists
SN 1477-9129
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/92140
UL https://hdl.handle.net/20.500.14352/92140
LA eng
NO Paraíso-Luna, J.; Aguareles, J.; Martín, R.; Ayo-Martín, A. C.; Simón-Sánchez, S.; García-Rincón, D.; Costas-Insua, C.; García-Taboada, E.; de Salas-Quiroga, A.; Díaz-Alonso, J.; Liste, I.; Sánchez-Prieto, J.; Cappello, S.; Guzmán, M.; Galve-Roperh, I. Endocannabinoid signalling in stem cells and cerebral organoids drives differentiation to deep layer projection neurons via CB(1) receptors. Development 2020, 147, dev192161. doi: 10.1242/dev.192161 
NO Ministerio de Educación, Cultura y Deporte (España)
NO Ministerio de Ciencia (España)
NO Ministerio de Sanidad (España)
NO European Commission
DS Docta Complutense
RD 11 abr 2025