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Publication

The Hippo Pathway Blocks Mammalian Retinal Müller Glial Cell Reprogramming.

Cell reports | 2019

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.

Pubmed ID: 31067451 RIS Download

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Associated grants

Agency: NHLBI NIH HHS, United States
Id: R01 HL118761
Agency: NHLBI NIH HHS, United States
Id: R01 HL127717
Agency: NEI NIH HHS, United States
Id: R01 EY030448
Agency: NIAID NIH HHS, United States
Id: P30 AI036211
Agency: NHGRI NIH HHS, United States
Id: U54 HG006348
Agency: NEI NIH HHS, United States
Id: R01 EY024906
Agency: NHLBI NIH HHS, United States
Id: F31 HL136065
Agency: NCI NIH HHS, United States
Id: P30 CA125123
Agency: NHGRI NIH HHS, United States
Id: UM1 HG006348
Agency: NHLBI NIH HHS, United States
Id: R01 HL130804
Agency: NCRR NIH HHS, United States
Id: S10 RR024574
Agency: NIDCR NIH HHS, United States
Id: R01 DE023177

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