NDE1-Mediated Regulation of Neural Progenitor Regional Identity and Its Implication in Microcephaly.

Loss of NDE1 disrupts neural progenitor regional identity in human brain organoids and mouse forebrains, causing a caudal identity shift linked to prolonged mitosis and altered patterning.

• Why it matters: The genetic and molecular bases of neurodevelopmental disorders, including NDE1-associated microcephaly, remain poorly understood, limiting mechanistic insight and targeted hypotheses.
• What they did: Using human brain organoids and Nde1 knockout mouse models, the study assessed progenitor identity, mitosis timing, and forebrain regional patterning, and tested ERK pathway activation to restore rostral PAX6.
• The result: NDE1 loss is linked to aberrant ERK signaling, and downstream ERK activation restored rostral PAX6 expression in human organoids, supporting NDE1’s role in early human brain regionalization.

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