Format

Send to

Choose Destination
Cell Rep. 2019 May 7;27(6):1637-1649.e6. doi: 10.1016/j.celrep.2019.04.047.

The Hippo Pathway Blocks Mammalian Retinal Müller Glial Cell Reprogramming.

Author information

1
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
2
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
3
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
4
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Heart Institute, Cardiomyocyte Renewal Lab, Houston, TX 77030, USA.
5
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Development, Disease Models and Therapeutics Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA; Genetics and Genomics Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA; Cardiovasular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA; Texas Heart Institute, Cardiomyocyte Renewal Lab, Houston, TX 77030, USA. Electronic address: jfmartin@bcm.edu.
6
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Development, Disease Models and Therapeutics Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA; Genetics and Genomics Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: poche@bcm.edu.

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.

KEYWORDS:

Hippo pathway; LATS; Müller glia; YAP; regeneration; reprogramming; retina

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center