Yap-lin28a axis targets let7-Wnt pathway to restore progenitors for initiating regeneration

Ye, Zhian; Su, Zhi; Xie, Siyu; Liu, Yuye; Wang, Yongqiang; Xu, Xi; Zheng, Yiqing; Zhao, Meng; Jiang, Linjia

doi:10.7554/elife.55771

Cited by 21 publications

(34 citation statements)

References 61 publications

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“…Hair cell injury to the chick utricle resulted in nuclear translocation of YAP1, but we did not observe this response in the mouse utricle, even after severe epithelial injury. These results, which are consistent with findings recently reported by other investigators [34][35][36][37] , suggest that the lack of YAP1 signaling following hair cell damage may be one factor that limits the regenerative ability of the mammalian ear.…”

Section: Discussionsupporting

confidence: 93%

Dynamic patterns of YAP1 expression and cellular localization in the developing and injured utricle

Borse

Barton

Arndt

et al. 2021

Sci Rep

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The Hippo signaling pathway is a key regulator of tissue development and regeneration. Activation of the Hippo pathway leads to nuclear translocation of the YAP1 transcriptional coactivator, resulting in changes in gene expression and cell cycle entry. Recent studies have demonstrated the nuclear translocation of YAP1 during the development of the sensory organs of the inner ear, but the possible role of YAP1 in sensory regeneration of the inner ear is unclear. The present study characterized the cellular localization of YAP1 in the utricles of mice and chicks, both under normal conditions and after HC injury. During neonatal development, YAP1 expression was observed in the cytoplasm of supporting cells, and was transiently expressed in the cytoplasm of some differentiating hair cells. We also observed temporary nuclear translocation of YAP1 in supporting cells of the mouse utricle after short periods in organotypic culture. However, little or no nuclear translocation of YAP1 was observed in the utricles of neonatal or mature mice after ototoxic injury. In contrast, substantial YAP1 nuclear translocation was observed in the chicken utricle after streptomycin treatment in vitro and in vivo. Together, these data suggest that differences in YAP1 signaling may partially account for the differing regenerative abilities of the avian vs. mammalian inner ear.

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Section: Discussionsupporting

confidence: 93%

Dynamic patterns of YAP1 expression and cellular localization in the developing and injured utricle

Borse

Barton

Arndt

et al. 2021

Sci Rep

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“…To support the idea that Yap is required for lin28a expression, evaluation of the lin28a promoter revealed a Tead1 binding motif (MatInspector software v3.13; data not shown), to which Yap typically binds ( Yu et al, 2015 ). This is also consistent with recent findings indicating that Yap directly binds to this region of the lin28a promoter in the context of the zebrafish-injured lateral line and that a Yap−Lin28a axis reprograms sensory hair cell precursors to generate Sox2-positive progenitors ( Ye et al, 2020 ). On the other hand, Sox2 has also been previously reported to promote MG reprogramming by controlling Lin28a and Ascl1 in the zebrafish regenerating retina ( Gorsuch et al, 2017 ).…”

Section: Discussionsupporting

confidence: 93%

Yap Regulates Müller Glia Reprogramming in Damaged Zebrafish Retinas

Lourenço

Brandão

Borbinha

et al. 2021

Front. Cell Dev. Biol.

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Vertebrates such as zebrafish have the outstanding ability to fully regenerate their retina upon injury, while mammals, including humans, do not. In zebrafish, upon light-induced injury, photoreceptor regeneration is achieved through reprogramming of Müller glia cells, which proliferate and give rise to a self-renewing population of progenitors that migrate to the lesion site to differentiate into the new photoreceptors. The Hippo pathway effector YAP was recently implicated in the response to damage in the retina, but how this transcription coactivator is integrated into the signaling network regulating Müller glia reprogramming has not yet been explored. Here, we show that Yap is required in Müller glia to engage their response to a lesion by regulating their cell cycle reentry and progenitor cell formation, contributing to the differentiation of new photoreceptors. We propose that this regulation is accomplished through a lin28a–ascl1a-dependent mechanism, bona fide Müller glia-reprogramming factors. Overall, this study presents Yap as a key regulator of zebrafish Müller glia reprogramming and consequently retina regeneration upon injury.

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“…Many of these genes have been implicated in regeneration, such as il11 that stimulates progenitor cells in axolotl tail regeneration, Jak/Stat3 and Nr4a1 target relaxin3a (rln3a) that is required for zebrafish heart regeneration (Figure 4G, (Fang et al, 2013; Tsujioka et al, 2017; You et al, 2018)). Likewise, the RNA binding protein Lin28 supports mouse axon regeneration, coordinates hair cell progenitor proliferation and differentiation and zebrafish hair cell regeneration (Doetzlhofer and Avraham, 2017; Wang et al, 2018; Ye et al, 2020). Lin28a also leads to enhanced tissue repair by metabolic reprogramming and increased glycolysis and oxidative phosphorylation in mice (Shyh-Chang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, the RNA binding protein Lin28 supports mouse axon regeneration, coordinates hair cell progenitor proliferation and differentiation and zebrafish hair cell regeneration (Doetzlhofer and Avraham, 2017;Wang et al, 2018;Ye et al, 2020).…”

Section: Regeneration Specific Genes Are Active Between 30min and 1hmentioning

confidence: 99%

High-resolution single cell transcriptome analysis of zebrafish sensory hair cell regeneration

Baek

Ntt

et al. 2021

Preprint

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Loss of sensory hair cells in the mammalian inner ear leads to permanent hearing and vestibular defects, whereas loss of hair cells in zebrafish results in their regeneration. We used scRNA-Seq to characterize the transcriptional dynamics of hair cell regeneration in zebrafish at unprecedented spatio-temporal resolution. We uncovered three, sequentially activated modules. First, an injury/inflammatory response and downregulation of progenitor/stem cell maintenance genes within minutes after hair cell loss. Second, the transient activation of regeneration-specific genes. And third, a robust reactivation of developmental gene programs, including hair cell specification, cell cycle activation, ribosome biogenesis, and a metabolic switch to oxidative phosphorylation. The results are not only relevant for our understanding of hair cell regeneration and how we might be able to trigger it in mammals but also for regenerative processes in general. The data is searchable and publicly accessible via a web-based interface.

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Yap-lin28a axis targets let7-Wnt pathway to restore progenitors for initiating regeneration

Cited by 21 publications

References 61 publications

Dynamic patterns of YAP1 expression and cellular localization in the developing and injured utricle

Dynamic patterns of YAP1 expression and cellular localization in the developing and injured utricle

Yap Regulates Müller Glia Reprogramming in Damaged Zebrafish Retinas

High-resolution single cell transcriptome analysis of zebrafish sensory hair cell regeneration

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