Figure 3.

The mechanism of PQBP1-linked microcephaly and the three major mechanisms of microcephaly published previously. (Upper left) In normal state, neurons are produced from neural stem cells at the constant differentiation rate. (Lower left) The microcephaly mechanism of PQBP1-cKO mice is shown. Due to the elongation of total cell cycle time, even though the differentiation rate is not changed, the total number of neurons produced from neural stem cells is reduced. The right side panels show previously known mechanisms of microcephaly. (Right upper) In the case where the differentiation rate to neurons is increased, the neural stem cell pool is depleted earlier than in normal state, and the total number of neurons produced from neural stem cells is reduced. (Right middle) When cell death of neural stem cells occurs, the total number of neurons produced from neural stem cells is reduced. (Right lower) When migration of differentiated neurons is impaired, the cortical layer structure becomes abnormal, and the abnormality leads to microcephaly.