ARFGEF2 and microcephaly: Interestingly, mutations in ArfGEF2/Big2 cause periventricular heterotopia (caused by the migration defect in neurons) and microcephaly (caused by the proliferation defect in neural progenitors) in humans, suggesting that ArfGEF2/Big2 and its downstream Arf family small GTPases are also involved in both neural progenitor proliferation and migration start, likely through the regulation of membrane trafficking [171].