Figure 9. Summary of changes in cellular and molecular kinetics due to loss of Notch signaling.
Cycling progenitor cells that receive a pulse of DAPT for 3h or less are able to recover and remain progenitors (A, white to gray), even though Notch effector genes have been downregulated (B). However exposure to periods of DAPT treatment for 6h or longer causes a permanent commitment to differentiate (large arrows). Committed progenitor cells increase expression of general differentiation genes by 12h, with a concomitant decrease in expression of progenitor genes and an increase in expression of cell-type specific genes by 24h. By 48h after Notch signaling inactivation, decreased proliferation and widespread neuronal differentiation are readily apparent. If Notch signaling is inactivated in early in development, then early cell types such as cones and ganglion cells are generated (as depicted). If Notch is inactivated during late retinal development, then increases in later cell types are observed, such as rods, along with conconmittent decreased Muller glia differentiation. The inherent cascade of proneural bHLH transcription factors initiated by synchronized Notch signaling inactivation underscores the temporal requirement for progenitor cells to permanently commit to neuronal differentiation.