PUBLICATION
Vegf signaling between Müller glia and vascular endothelial cells is regulated by immune cells and stimulates retina regeneration
- Authors
- Mitra, S., Devi, S., Lee, M.S., Jui, J., Sahu, A., Goldman, D.
- ID
- ZDB-PUB-221206-10
- Date
- 2022
- Source
- Proceedings of the National Academy of Sciences of the United States of America 119: e2211690119e2211690119 (Journal)
- Registered Authors
- Goldman, Dan
- Keywords
- Notch, Pgf, neurodegeneration, reprogramming, stem cell
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Proliferation/physiology
- Endothelial Cells/metabolism
- Ependymoglial Cells/metabolism
- Mammals/metabolism
- Nerve Regeneration/physiology
- Neuroglia/metabolism
- Regeneration/physiology
- Retina/metabolism
- Signal Transduction
- Zebrafish*/metabolism
- Zebrafish Proteins*/metabolism
- PubMed
- 36469778 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Mitra, S., Devi, S., Lee, M.S., Jui, J., Sahu, A., Goldman, D. (2022) Vegf signaling between Müller glia and vascular endothelial cells is regulated by immune cells and stimulates retina regeneration. Proceedings of the National Academy of Sciences of the United States of America. 119:e2211690119e2211690119.
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. Cell43, 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping