Overview
- Researchers used CRISPR-Cas9 in human cortical neuron models to show ZNF804A is most active early in development and is concentrated in glutamatergic cortical neurons.
- Reducing ZNF804A function increased ribosome presence and protein translation in dendrites, producing more synaptic proteins and a higher number of synapses on those neurons.
- Neurons with impaired ZNF804A showed greater electrical responses when chemically stimulated, indicating the genetic change raises neuronal excitability.
- The work establishes a mechanistic link between ribosome localization, local protein synthesis, and synaptogenesis for a schizophrenia risk gene, connecting prior separate findings about ZNF804A.
- Authors note the experiments are targeted, single-gene manipulations in vitro funded by UK research bodies, and they call for replication, multi-gene scaling and in vivo work to test whether many risk loci converge on shared pathways.