Id2 transcriptional repressor promotes retinal Müller glial cell fate choice by increasing Notch activity

In the vertebrate retina, Müller glial cells and neurons originate from common progenitor cells. To identify the genes that regulate the cell fate choice of Müller glial cells from retinal progenitor cells, we first generated Rlbp1-EGFP transgenic mice in which differentiating Müller glia were specifically labeled with EGFP. By performing fluorescence-activated cell sorting and RNA sequencing analysis, we found that Id1, Id2, and Id3, were highly enriched in developing and differentiated Müller glial cells. While Id1/2/3 are inhibitory helix-loop-helix (HLH) transcription factors, the functional role and underlying mechanism of each Id protein in Müller glial cell development are not fully understood. In situ hybridization revealed Id1/2/3 expression in the layer where retinal progenitor cells and Müller glial cells reside in developing and adult retinas, respectively. Cell lineage analysis using retroviruses expressing Id1, Id2, or Id3 showed that Id2 possesses a stronger inducing activity in Müller glial cell fate choice than Id1 and Id3. Co-immunoprecipitation and luciferase reporter analyses suggested that Id2 interacts with the Notch intracellular region and promotes Notch activity. Taken together, these results suggest that Id2 promotes Müller glial cell fate choice by increasing Notch activity in the developing mouse retina.