Development· 2026Q1
Loss of PAX6 alters the excitatory/inhibitory neuronal ratio in human cerebral organoids
- 2citations
- Q1SCImago
- 2026year
Short summary
Human cerebral organoids lacking the PAX6 gene show an increased ratio of inhibitory to excitatory neurons, with excitatory neurons exhibiting delayed maturation and altered gene expression.
AI-generated from the title and abstract; the full text is not read.
Key points
- Homozygous PAX6 mutant (PAX6-/-) human cerebral organoids were larger than controls.
- PAX6-/- organoids showed an increased number of inhibitory neurons.
- Excitatory neurons in PAX6-/- organoids were less mature and some expressed inhibitory identity genes.
- The altered excitatory/inhibitory ratio in PAX6-/- organoids was linked to dysregulated PTN-PTPRZ1 signaling.
AI-generated from the title and abstract; the full text is not read.
Abstract
The transcription factor PAX6 is a crucial regulator of multiple aspects of embryonic forebrain development. It has well-established roles in the regulation of excitatory and inhibitory neuron development in the embryonic cortex in mice but PAX6's roles during human forebrain development are less well understood. Using human cerebral organoids, we investigated PAX6's roles in human neurodevelopment. Homozygous PAX6 mutant (PAX6-/-) organoids were larger than controls and contained increased inhibitory cell types. Excitatory neurons were still generated in PAX6-/- organoids but they were less mature, and a subset showed dysregulated expression of inhibitory identity genes compared to PAX6+/+ controls. The inhibitory cells found in PAX6-/- organoids physically segregated from excitatory neurons and presented a distinct transcriptomic profile when compared to in vivo cortical inhibitory neurons. PAX6-/- organoids showed a dysregulated cellular response to PTN-PTPRZ1 signalling, which contributed to the observed increase in inhibitory neurons and the consequent altered excitatory to inhibitory neuronal ratio.
The authors' abstract, as published at the source. Development, 2026 · DOI ↗
Continue with a free account
Ask the paper: 3 free questions a day about this paper; save it, get its citation, new summaries every day for your field. Takeaways are Premium.
Continue free on the webSign in with Google or Apple; no card needed. You come back to this paper.
On your phone:
Field: Developmental Neuroscience
Developmental NeuroscienceNeuroscience