Language
English
Publication Date
6-1-2026
Journal
PNAS Nexus
DOI
10.1093/pnasnexus/pgag188
PMID
42318179
PMCID
PMC13273572
PubMedCentral® Posted Date
5-28-2026
PubMedCentral® Full Text Version
Post-print
Abstract
The Hippo pathway effector YAP promotes spontaneous proliferation of Müller glia (MG), suggesting that bypassing Hippo signaling and activating YAP could enhance retinal regeneration. However, whether proliferative adult MGs retain meaningful neurogenic competence remains unclear. Here, using viral delivery of a Hippo-resistant YAP variant to wild-type adult MGs, we achieved transient YAP activation in adult MGs, inducing proliferation followed by cell-cycle withdrawal and differentiation. Intersectional genetic lineage tracing and EdU labeling, combined with transcriptomic analyses, revealed that YAP-activated MGs predominantly regenerate MGs, whereas only a subset gives rise to bipolar cell-like neurons. These results indicate that proliferative MGs acquire a state resembling that of late-stage retinal progenitors, with limited neurogenic lineage potential. We conclude that YAP-activated cell-cycle reentry inefficiently reprograms adult MGs toward photoreceptor or ganglion cell fates. These findings define the limited competence of proliferative adult MGs to contribute to neurogenic fates and provide a rigorous framework for assessing in vivo glial reprogramming strategies.
Keywords
regeneration, mammalian retina, Müller glia, Hippo signaling, AAV
Published Open-Access
yes
Recommended Citation
Laserna, English J; Saltykova, Irina V; Hall, Benjamin M; et al., "Transient Yap Activation Uncovers the Neurogenic Potential of Proliferative Mammalian Müller Glia" (2026). Faculty, Staff and Students Publications. 7177.
https://digitalcommons.library.tmc.edu/baylor_docs/7177