Summary
Published in Molecular Brain (2026), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Havusha-Laufer, Sapir, et al. Altered ECM deposition and cell adhesion signaling in a human cortical organoid model of fragile X syndrome
Altered ECM deposition and cell adhesion signaling in a human cortical organoid model of fragile X syndrome
Research Overview
Fragile X Syndrome is the most common inherited intellectual disability and the most common single-gene cause of autism. It arises when the FMR1 gene is epigenetically silenced, removing FMRP — an RNA-binding protein that controls local protein synthesis in dendrites during synapse development. Brain organoids grown from pluripotent stem cells offer a way to study the mechanism in human tissue.
The authors generated Fragile X and control cortical organoids from isogenic human embryonic stem cell clones differing only in the FXS mutation, and found that mature FXS cortical organoids could be derived by inhibiting the TGFβ and Wnt pathways. Immunofluorescence, qRT-PCR, proteomics, and western blotting then compared the two, pointing to altered extracellular-matrix deposition and cell-adhesion signaling in the disease organoids.
Key Discoveries
- Isogenic human ESC clones with and without the FXS mutation yielded matched cortical organoids
- Mature FXS cortical organoids obtained by inhibiting TGFβ and Wnt signaling
- Multi-omic comparison implicated altered ECM deposition and cell-adhesion signaling in Fragile X
