Notch signaling via Hey1 and Id2b regulates Müller glia's regenerative response to retinal injury

Unlike mammals, zebrafish can regenerate a damaged retina. Key to this regenerative response are Müller glia (MG) that divide and produce progenitors for retinal repair. Although factors regulating MG’s decision to divide remain mostly unknown, a certain threshold of neuron death must be exceeded in order for MG to engage in a regenerative response. A role for Notch signaling in this process is indicated since its inhibition expands the zone of injury-responsive MG following a focal injury. Our data show that injury-dependent changes in Dll4 and Dlb control Notch signaling in MG and that Hey1 and Id2b are downstream effectors that regulate proliferation of MG and MG-derived progenitors. Although we find Hey1 and Id2b can inhibit proliferation of MG-derived progenitors, only Hey1 is able to regulate MG's injury response threshold. Remarkably, Hey1 suppression is sufficient to recapitulate the effects of Notch inhibition on MG’s injury response threshold.