Transient disruption of progenitor states and layer 2/3 projection neuron generation in frontal association cortex due to 22q11.2 gene deletion

Transient disruption of progenitor states in the fetal frontal cortex due to 22q11.2 gene deletion reduces Layer 2/3 projection neuron generation by 22-50%, impacting cortical connectivity.

• Why it matters: Understanding how genetic deletions affect specific neuron populations is crucial for unraveling the developmental origins of schizophrenia and related disorders linked to 22q11.2 Deletion Syndrome.
• What they did: The study examined fetal mouse models with 22q11.2 deletion, analyzing cell states, gene expression, and DNA methylation in progenitors and neuroblasts during peak neurogenesis, focusing on Layer 2/3 neuron development.
• The result: Findings reveal a narrow developmental window where progenitor states are altered, leading to a significant decline and molecular divergence of Layer 2/3 projection neurons in the frontal association cortex, highlighting potential targets for intervention.