Fig. 10. A signaling network of Hdac1, Wnt and Notch in zebrafish retinal neurogenesis. (A) Retinal phenotypes produced by different combinations of Wnt and Hdac1 activities. Squares that represent 2 dpf retinal phenotypes (red, proliferation; blue, cell-cycle exit) are plotted at positions where combinations of Hdac and Wnt activities intersect. The broken line is a theoretical borderline between `proliferation' and `cell-cycle exit'. (B) The canonical Wnt signaling promotes the cell-cycle progression and Notch signaling inhibits neurogenesis through the activation of her4/Hes5 in the zebrafish retina. In this study, we found that Notch signaling is involved in the maintenance of proliferation of retinal cells. Hdac1 antagonizes Wnt and Notch signaling pathways to promote the cell-cycle exit and subsequent neurogenesis in the zebrafish retina. Because a balance between Wnt signaling and Hdac activity correlates with the ratio of proliferation to differentiation, one theory is that the competition between ß-catenin and Hdac1 determines whether retinal cells continue to proliferate or exit from the cell cycle. Although it is generally accepted that, following Notch activation, the CSL co-repressor complex containing Hdac is displaced by a co-activator complex coordinated by NICD (Lai, 2004), it remains to be elucidated whether a balance between NICD and Hdac1 activities regulates Notch-mediated proliferation and neurogenic inhibition in the zebrafish retina.