Fig. 8. Explanation of the most probable cause of the differences observed in the cultures (Fig. 7). (A) In wild-type cells, the data are compatible with cells having a cell-cycle time of around 12 hours, as has been shown previously in vivo (Takahashi et al., 1995b) (present study). Some cells are in S-phase during the 45 minute BrdU pulse and incorporate BrdU (filled circle); others will enter S-phase after the BrdU pulse or are postmitotic and will not label with BrdU (open circles). One in five cells are BrdU labelled following the pulse (i.e. 20%; compare with wild-type data at 12.75 hours in Fig. 7A). As the cells containing BrdU divide (thick lines), the proportion of BrdU-labelled cells in the culture increases. Once the nonlabelled cells divide (thin lines), the proportion of BrdU-labelled cells will decrease again. This trend is seen for wild-type data in Fig. 7A. Broken lines indicate cells that are postmitotic. Three in five cells are postmitotic at the time of the BrdU pulse (i.e. 60%; compare with wild-type data at 12.75 hours in Fig. 7D) and if half the divisions that occur in culture produce postmitotic neurones (shown as a broken line originating from the nonlabelled cell, although it could originate from the labelled cell), then roughly the same number will be postmitotic at 24 hours (four in seven cells, i.e. 57%; compare with wild-type data at 24 hours in Fig. 7D). The proportions of postmitotic cells and progenitor cells will not change greatly during culture in the scheme illustrated. (B) An interpretation of events in cultures of Pax6^Sey/Sey cells is shown, using the same conventions as in A. A shorter cell cycle produces an initially higher proportion of BrdU-labelled cells (filled circles; two in five cells, or 40%; compare with data from mutants in Fig. 7A) and a subsequent steady increase in these proportions (four in seven cells at 18 hours; six in ten cells at 24 hours). This models the steady increase seen for mutant cells in Fig. 7A. The scheme illustrated, in which divisions produce one progenitor and one postmitotic cell, will lead to an abnormally rapid decrease in the proportions of progenitors and an increase in the proportions of postmitotic cells (from 40% at the time of the BrdU pulse to 70% at 24 hours; comparable with data from mutants in Fig. 7D).

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