Article Dans Une Revue Nature Methods Année : 2024

A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids

Camilla Bosone
  • Fonction : Auteur
Davide Castaldi
  • Fonction : Auteur
Thomas Rainer Burkard
Segundo Jose Guzman
Cristina Cheroni
  • Fonction : Auteur
Nicolò Caporale
Sunanjay Bajaj
  • Fonction : Auteur
Joshua Adam Bagley
Chong Li
Carlo Emanuele Villa
  • Fonction : Auteur
Giuseppe Testa
Veronica Krenn
Jürgen Arthur Knoblich

Résumé

Organoids generating major cortical cell types in distinct compartments are used to study cortical development, evolution and disorders. However, the lack of morphogen gradients imparting cortical positional information and topography in current systems hinders the investigation of complex phenotypes. Here, we engineer human cortical assembloids by fusing an organizer-like structure expressing fibroblast growth factor 8 (FGF8) with an elongated organoid to enable the controlled modulation of FGF8 signaling along the longitudinal organoid axis. These polarized cortical assembloids mount a position-dependent transcriptional program that in part matches the in vivo rostrocaudal gene expression patterns and that is lost upon mutation in the FGFR3 gene associated with temporal lobe malformations and intellectual disability. By producing spatially oriented cell populations with signatures related to frontal and temporal area identity within individual assembloids, this model recapitulates in part the early transcriptional divergence embedded in the protomap and enables the study of cortical area-relevant alterations underlying human disorders.

Dates et versions

hal-04799215 , version 1 (22-11-2024)

Identifiants

Citer

Camilla Bosone, Davide Castaldi, Thomas Rainer Burkard, Segundo Jose Guzman, Tom Wyatt, et al.. A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids. Nature Methods, 2024, 21 (11), pp.2147-2159. ⟨10.1038/s41592-024-02412-5⟩. ⟨hal-04799215⟩
45 Consultations
0 Téléchargements

Altmetric

Partager

  • More