Affiliation:
1. Michigan Neuroscience Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109
Abstract
In the zebrafish retina, Müller glia (MG) can regenerate retinal neurons lost to injury or disease. Even though zebrafish MG share structure and function with those of mammals, only in zebrafish do MG function as retinal stem cells. Previous studies suggest dying neurons, microglia/macrophage, and T cells contribute to MG’s regenerative response [White et al.,
Proc. Natl. Acad. Sci. U.S.A.
114
, E3719 (2017); Hui et al.,
Dev. Cell
43
, 659 (2017)]. Although MG end-feet abut vascular endothelial (VE) cells to form the blood–retina barrier, a role for VE cells in retina regeneration has not been explored. Here, we report that MG-derived Vegfaa and Pgfa engage Flt1 and Kdrl receptors on VE cells to regulate MG gene expression, Notch signaling, proliferation, and neuronal regeneration. Remarkably,
vegfaa
and
pgfa
expression is regulated by microglia/macrophages, while Notch signaling in MG is regulated by a Vegf-
dll4
signaling system in VE cells. Thus, our studies link microglia/macrophage, MG, and VE cells in a multicomponent signaling pathway that controls MG reprogramming and proliferation.
Funder
Gilbert Family Foundation
HHS | NIH | National Eye Institute
Publisher
Proceedings of the National Academy of Sciences
Cited by
8 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献