The Retinal Pigment Epithelium Is a Notch Signaling Niche in the Mouse Retina

Publication date: 11 April 2017
Source:Cell Reports, Volume 19, Issue 2
Author(s): Taejeong Ha, Kyeong Hwan Moon, Le Dai, Jun Hatakeyama, Keejung Yoon, Hee-Sae Park, Young-Yoon Kong, Kenji Shimamura, Jin Woo Kim
Notch signaling in neural progenitor cell is triggered by ligands expressed in adjacent cells. To identify the sources of active Notch ligands in the mouse retina, we negatively regulated Notch ligand activity in various neighbors of retinal progenitor cells (RPCs) by eliminating mindbomb E3 ubiquitin protein ligase 1 (Mib1). Mib1-deficient retinal cells failed to induce Notch activation in intra-lineage RPCs, which prematurely differentiated into neurons; however, Mib1 in post-mitotic retinal ganglion cells was not important. Interestingly, Mib1 in the retinal pigment epithelium (RPE) also contributed to Notch activation in adjacent RPCs by supporting the localization of active Notch ligands at RPE-RPC contacts. Combining this RPE-driven Notch signaling and intra-retinal Notch signaling, we propose a model in which one RPC daughter receives extra Notch signals from the RPE to become an RPC, whereas its sister cell receives only a subthreshold level of intra-retinal Notch signal and differentiates into a neuron.

Graphical abstract

Teaser

Ha et al. identify a role of retinal pigment epithelium (RPE) as a Notch signaling niche in the mouse retina. The extra Notch signal derived from the RPE is especially critical to maintaining the RPC fate of cells that receive an insufficient Notch signal from their sister cells.


http://ift.tt/2oz7JJg