Summary
A bioRxiv preprint reports that cerebral organoids cultured for more than six months reproduce a pattern of interneuron migration seen in the postnatal human cortex. The researchers used imaging, transcriptomics and gene perturbations to investigate how the cells move and organize.
A bioRxiv preprint reports that cerebral organoids cultured for more than six months reproduce a pattern of interneuron migration found in the postnatal human cortex. Using live imaging, mathematical modelling and gene-expression analyses, the researchers examined how these neurons move and form organized streams.
Interneurons are a class of neurons involved in local brain circuits. The authors describe late-born interneurons migrating into the cortex after birth in humans, a process they say is absent in rodents. That difference has made the process difficult to study experimentally in animals.
How the organoids model migration
The researchers found that interneurons in the organoids migrate in chains. Their analyses suggest that the cells’ ability to move in chains is intrinsic, while interactions with astrocytes—another type of brain cell—help organize the chains into streams.
Spatial and single-cell transcriptomic analyses identified a molecular signature specific to the human postnatal migratory streams. That signature was enriched for genes associated with neurodevelopmental disorders. The team also perturbed the autism-associated genes CNTN5 and FGF14; the interventions disrupted chain organization and migration in different ways.
A model for a difficult-to-study stage
The findings suggest that long-term cerebral organoid cultures can provide an experimental model for investigating this particular aspect of postnatal human brain development. The authors say the system could enable mechanistic and genetic studies of the migration process, which is difficult to examine in rodents.
The work is a bioRxiv preprint, so its findings have not yet undergone peer review. It concerns a specific developmental process in organoids, rather than the full complexity of postnatal brain development. The preprint also discloses that senior author Juergen A. Knoblich holds patents related to cerebral-organoid technology and is a co-founder and scientific advisory board member of a:head bio AG.