Fig. 9. A model of signal convergence in retinal progenitor cells. DELTA-NOTCH signaling yields the NOTCH intracellular domain (NICD) and activates HES1 transcription. SHH signaling through patched (PTC) and Smoothened (SMO) reduces Gli repressor (Gli^Rep) and facilitates the accumulation of the Gli activator (Gli^Act). SHH signaling upregulates HES1 by unknown mechanism(s). VEGF stimulation causes the activation of the MEK-ERK cascade and enhances HES1 activity without the involvement of MEK1/2 function. The promotion of cell proliferation may require independent inputs from both MEK-ERK and HES1, whereas suppression of RGC specification mainly involves HES1 activity. Therefore, HES1 serves as a node of signal convergence to integrate inputs of multiple cell-extrinsic cues.