Born early, built wrongly: Outer radial glia in ASPM-mediated microcephaly.

ASPM mutations in human cortical organoids randomize spindle orientation precociously and prevent functional outer radial glia formation, pointing to a species-specific mechanism.

• Why it matters: Human cortical development can diverge from mouse models, leaving unclear which cellular behaviors underlie microcephaly-related differences across species.
• What they did: Limame et al. tested ASPM-mutant human cortical organoids, measuring early spindle orientation and assessing whether outer radial glia become functional.
• The result: The findings link premature spindle misorientation to failure of functional outer radial glia in this human model, helping explain why mouse and human phenotypes may differ.

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