Temporal regulation of progenitor lineage progression and output by NFIs underlying human neocortical malformation.

NFIs act as conserved global temporal regulators of radial glial progenitor development, with mutations causing bidirectional impairments linked to human neocortical malformations.

• Why it matters: Understanding how NFIs influence brain development is crucial because their misexpression is associated with severe cortical malformations, yet the mechanisms remain unclear.
• What they did: Researchers used human cerebral organoids with patient-mimicking NFI mutations and mouse models with NFI manipulation to study RGP lineage progression and lifespan, revealing expression-dependent effects.
• The result: NFIs regulate RGP temporal development, with mutations causing overgrowth or premature differentiation, highlighting their role in normal neocortical formation and potential targets for addressing malformations.