Fig. 9. Model of Notch activity in retinal development. Notch is expressed in cycling retinal progenitor cells, where it can be proteolytically processed to form an intracellular fragment, NICD, following its interaction with a Notch ligand. The level of NICD-mediated signal that is finally transduced is read by a progenitor cell to determine the mitotic fate of the daughter cells. If the signal is below a threshold for cycling, at least one postmitotic daughter will be made. If the signal is above physiological levels for cycling, early progenitor cells do not continue to cycle, but they also do not make neurons (Dorsky et al., 1995) (A.P.J. and C.L.C., unpublished). If a postmitotic daughter is made, the level of Notch signaling is a determinate of the fate of the postmitotic daughter. If the Notch signal level is very low, as is the case in a complete loss of function, a photoreceptor is made, probably through activation of Otx2 (Nishida et al., 2003). If the level is intermediate, a non-photoreceptor neuron is made. The type of non-photoreceptor neuron is determined by the combination of homeobox and bHLH proteins present in the progenitor and/or newly postmitotic cell (Hatakeyama and Kageyama, 2004).