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The Hippo Pathway Blocks Mammalian Retinal Müller Glial Cell Reprogramming
- Source :
- Cell reports, Cell Reports, Vol 27, Iss 6, Pp 1637-1649.e6 (2019)
- Publication Year :
- 2018
-
Abstract
- SUMMARY 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.<br />In Brief Rueda et al. identify the Hippo pathway as an endogenous molecular mechanism normally preventing mammalian Müller glial reprogramming to a proliferative, progenitor-like state.<br />Graphical Abstract
- Subjects :
- 0301 basic medicine
animal structures
Ependymoglial Cells
Cell Cycle Proteins
Protein Serine-Threonine Kinases
General Biochemistry, Genetics and Molecular Biology
Retina
Article
03 medical and health sciences
Mice
0302 clinical medicine
Downregulation and upregulation
medicine
Animals
Cyclin D1
Hippo Signaling Pathway
Cyclin D3
lcsh:QH301-705.5
Zebrafish
Adaptor Proteins, Signal Transducing
Cell Proliferation
Mammals
Hippo signaling pathway
biology
Stem Cells
fungi
YAP-Signaling Proteins
Cell cycle
biology.organism_classification
Cellular Reprogramming
Cell biology
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
Hippo signaling
sense organs
Reprogramming
Muller glia
Neuroglia
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 27
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cell reports
- Accession number :
- edsair.doi.dedup.....a51dd93deb4776d2a3b03432ad20390a