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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1995) (A.P.J. and C.L.C., unpublished).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).
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