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

ABSTRACT: 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 malformation

SUBMITTER: Bosone C 

PROVIDER: S-EPMC11541204 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature