Distinct domains of Oligophrenin-1 regulate successive phases of cortical radial migration via RHOA- and PACSIN2-dependent mechanisms.

Oligophrenin-1 (OPHN1) coordinates successive phases of cortical radial migration by using its GAP domain to suppress RHOA-ROCK for MP-to-BP and its proline-rich domain for locomotion remodeling.

• Why it matters: Circuit assembly depends on orderly excitatory neuron migration, but how molecular control is coordinated across MP-to-BP and radial glial-guided locomotion remains unclear.
• What they did: Using molecular replacement plus live-cell imaging, the study tests how OPHN1 domains regulate migration, linking the GAP domain to RHOA-ROCK suppression and the second proline-rich domain to PACSIN2-dependent leading process remodeling and nucleokinesis.
• The result: Domain-specific OPHN1 functions are linked to stepwise control of radial migration during corticogenesis, supporting a dual role in early cortical development through RHOA- and PACSIN2-dependent mechanisms.

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