Mutations in a brain-growth gene reveal the price of a larger human cortex: less room for timing errors.

The Story

Human ASPM mutations cut cortical growth by disrupting neural stem cells; other mammals differ in how their developing cortex uses the same gene.

Human cortical growth depends on a finely timed supply of neural progenitors. The originating study reports that ASPM mutations disrupt this process in human cells, while comparative work shows that the effect varies sharply by species. Mice are relatively resistant, but ferrets reproduce the human-like microcephaly phenotype, making developmental architecture, not simply the presence of ASPM, the central explanation.

• MechanismASPM helps maintain divisions that expand neural progenitors; disruption reduces the cells available to build the cortex.
• Species differenceMouse and ferret results show that the same gene can have different consequences in brains with different developmental programs.
• Medical valueMapping the vulnerable human cell process could improve models of microcephaly and guide future treatment research.

• The originating study links ASPM mutations to premature disruption of human cortical progenitors, explaining reduced brain growth and microcephaly.medicalxpress +1
• ASPM supports spindle function and symmetric proliferative divisions in neural stem and progenitor cells.nature +1
• Aspm knockout causes few brain effects in mice but produces human-like microcephaly in ferrets, whose brains have larger, folded cortices.nature +1