To test this, we examined the expression of the precursor marker sox2. At 4 dpf in wild-type larvae, sox2 expression was limited to a few cells bordering the spinal cord central canal. By contrast, many spinal cord cells bordering the central canal and medial septum of pes mutant larvae expressed sox2, Riociguat BAY 63-2521 consistent with the idea that pes function in necessary for neural precursors to progress through the cell cycle and differentiate. pes was first identified in a zebrafish insertional mutagenesis screen on the basis of its loss-of-function phenotype. Schizandrin-B Subsequently, human cancer cell lines were found to express the homologous gene, PES1, at elevated levels and PES1 overexpression induced transformation of non-tumorogenic fibroblast cell lines, thus raising the possibility that Pes proteins promote cell proliferation. Consistent with this, yeast cells lacking function of Yph1p, the yeast pes homolog, underwent cell cycle arrest, Pes1 mutant mouse embryos arrested as early as the eight-cell stage and knockdown of pes1 function by RNAi in two breast cancer cell lines resulted in a significant inhibition of cell growth. In yeast, Yph1p, also known as Nop7p, is required for ribosome biogenesis, suggesting that loss of Yph1p function resulted in cell cycle arrest because of ribosome depletion. However, Yph1p can interact with many proteins that regulate cell cycle progression, particularly those that are active during S-phase. In the absence of Yph1p function, yeast cells released from hydroxyurea-induced arrest proceeded through S-phase at a significantly slower rate than normal. Consistent with this result, we observed a dramatic elongation of the cell cycle, and S-phase in particular, in the spinal cords of pes mutant zebrafish. However, the mechanism by which Pes regulates the cell cycle has yet to be elucidated. One possibility is that Pes directly regulates cell cycle progression through its interaction with MEC1, the yeast ATM/ ATR homologue, which regulates cell cycle checkpoint control. Pes also interacts with CDC28, the yeast cyclin dependant kinase and a known regulator of cell cycle progression. Therefore, the failure of neural precursors to progress normally through the cell cycle in pes mutant zebrafish may reveal a specific role for Pes in cell cycle regulation.