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The Hippo Pathway Blocks Mammalian Retinal Müller Glial Cell Reprogramming
Elda M Rueda1, Benjamin M Hall2, Matthew C Hill3
1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
Cell Reports
|May 9, 2019
Summary
Mammalian Müller glial cells (MGs) normally cannot regenerate retinal neurons. Repressing the Hippo signaling pathway unlocks their latent regenerative capacity, enabling proliferation and reprogramming.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Zebrafish Müller glial cells (MGs) regenerate retinal neurons after damage.
- Mammalian MGs lack this regenerative ability.
- The Hippo pathway's role in blocking mammalian MG regeneration is unknown.
Purpose of the Study:
- To investigate the regulatory mechanisms preventing mammalian MG proliferation and reprogramming.
- To identify potential strategies for stimulating retinal regeneration in mammals.
Main Methods:
- Investigated the Hippo pathway and its target YAP in mammalian MGs.
- Utilized MG-specific deletion of Hippo components (Lats1/Lats2).
- Employed transgenic expression of a Hippo non-responsive YAP (YAP5SA).
Main Results:
- Hippo pathway-mediated YAP repression blocks mammalian MG proliferation.
- Deletion of Lats1/Lats2 or YAP5SA expression induced Cyclin D1 upregulation.
- These manipulations led to loss of MG identity and a progenitor-like state.
Conclusions:
- Mammalian MGs possess latent regenerative capacity.
- Repressing Hippo signaling can stimulate MG proliferation and reprogramming.
- This finding offers a potential therapeutic avenue for retinal regeneration.
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