Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output.
Nat Neurosci
; 22(4): 669-679, 2019 04.
Article
de En
| MEDLINE
| ID: mdl-30886407
ABSTRACT
Neural organoids have the potential to improve our understanding of human brain development and neurological disorders. However, it remains to be seen whether these tissues can model circuit formation with functional neuronal output. Here we have adapted air-liquid interface culture to cerebral organoids, leading to improved neuronal survival and axon outgrowth. The resulting thick axon tracts display various morphologies, including long-range projection within and away from the organoid, growth-cone turning, and decussation. Single-cell RNA sequencing reveals various cortical neuronal identities, and retrograde tracing demonstrates tract morphologies that match proper molecular identities. These cultures exhibit active neuronal networks, and subcortical projecting tracts can innervate mouse spinal cord explants and evoke contractions of adjacent muscle in a manner dependent on intact organoid-derived innervating tracts. Overall, these results reveal a remarkable self-organization of corticofugal and callosal tracts with a functional output, providing new opportunities to examine relevant aspects of human CNS development and disease.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Organoïdes
/
Cortex cérébral
/
Techniques de culture de tissus
/
Neurones
Limites:
Female
/
Humans
/
Male
Langue:
En
Journal:
Nat Neurosci
Sujet du journal:
NEUROLOGIA
Année:
2019
Type de document:
Article
Pays d'affiliation:
Royaume-Uni