PUBLICATION
The Hippo Pathway Blocks Mammalian Retinal Müller Glial Cell Reprogramming
- Authors
- Rueda, E.M., Hall, B.M., Hill, M.C., Swinton, P.G., Tong, X., Martin, J.F., Poché, R.A.
- ID
- ZDB-PUB-190509-9
- Date
- 2019
- Source
- Cell Reports 27: 1637-1649.e6 (Journal)
- Registered Authors
- Keywords
- Hippo pathway, LATS, Müller glia, YAP, regeneration, reprogramming, retina
- MeSH Terms
-
- Stem Cells/metabolism
- Cell Proliferation
- Ependymoglial Cells/cytology*
- Ependymoglial Cells/enzymology*
- Cyclin D3/metabolism
- Adaptor Proteins, Signal Transducing/metabolism
- Signal Transduction*
- Mammals/metabolism*
- Retina/cytology*
- Mice
- Cell Cycle Proteins/metabolism
- Cellular Reprogramming*
- Protein Serine-Threonine Kinases/metabolism*
- Animals
- Cyclin D1/metabolism
- Neuroglia/cytology*
- Neuroglia/enzymology*
- PubMed
- 31067451 Full text @ Cell Rep.
Citation
Rueda, E.M., Hall, B.M., Hill, M.C., Swinton, P.G., Tong, X., Martin, J.F., Poché, R.A. (2019) The Hippo Pathway Blocks Mammalian Retinal Müller Glial Cell Reprogramming. Cell Reports. 27:1637-1649.e6.
Abstract
In response to retinal damage, the Müller glial cells (MGs) of the zebrafish retina have the ability to undergo a cellular reprogramming event in which they enter the cell cycle and divide asymmetrically, thereby producing multipotent retinal progenitors capable of regenerating lost retinal neurons. However, mammalian MGs do not exhibit such a proliferative and regenerative ability. Here, we identify Hippo pathway-mediated repression of the transcription cofactor YAP as a core regulatory mechanism that normally blocks mammalian MG proliferation and cellular reprogramming. MG-specific deletion of Hippo pathway components Lats1 and Lats2, as well as transgenic expression of a Hippo non-responsive form of YAP (YAP5SA), resulted in dramatic Cyclin D1 upregulation, loss of adult MG identity, and attainment of a highly proliferative, progenitor-like cellular state. Our results reveal that mammalian MGs may have latent regenerative capacity that can be stimulated by repressing Hippo signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping