A reciprocal regulatory loop between TAZ/YAP and G-protein Gαs regulates Schwann cell proliferation and myelination

Deng, Yaqi; Wu, Lai Man Natalie; Bai, Shujun; Zhao, Chuntao; Wang, Haibo; Wang, Jincheng; Xu, Lei; Sakabe, Masahide; Zhou, Wenhao; Xin, Mei; Lü, Qian

doi:10.1038/ncomms15161

Cited by 78 publications

(118 citation statements)

References 65 publications

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“…Prior to analysing potential ocular phenotypes in Yap +/mice, we wanted to confirm that the observed Yap expression reduction actually leads to the decrease of Yap target gene expression. Indeed, this may not be the case since compensatory regulation mechanisms have previously been reported between YAP and TAZ (Miesfeld et al, 2015;Deng et al, 2017;Neto et al, 2018). In accordance with this, we observed an increase in Taz transcript abundance in post-natal Yap +/retinas compared to controls ( Figure 1D).…”

Section: Compensatory Taz Regulation In Yap +/Post-natal Micesupporting

confidence: 85%

Yaphaploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy

Masson

García-García

Bitard

et al. 2020

Preprint

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Main PointsThis study finds unsuspected dynamics of YAP compensatory mechanisms in the retina of Yap +/mice Yap haploinsufficiency results in Müller glia dysfunction in aged mice, leading to lateonset cone dystrophy Post-natal Aged TAZ compensatory mechanism No TAZ compensatory mechanism Müller cell homeostasis dysfunction Delayed cell cycle exit Retinal progenitors Cone dystrophy Yap haploinsufficiency Taz upregulation Yap +/-Yap +/- ABSTRACTHippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine its function in adult neural retina, where YAP expression is restricted to Müller glia. We first discovered an unexpected temporal dynamic of gene compensation. At post-natal stages, Taz upregulation occurs, leading to a gain of function-like phenotype characterized by EGFR signalling potentiation and delayed cell cycle exit of retinal progenitors. In contrast, Yap +/adult retinas no longer exhibit TAZ-dependent dosage compensation. In this context, Yap haploinsufficiency in aged individuals results in Müller glia dysfunction, late-onset cone degeneration and reduced cone-mediated visual response. Alteration of glial homeostasis and altered patterns of cone opsins were also observed in Müller cell specific conditional Yap knockout mice. Together, this study highlights a novel YAP function in Müller cells for the maintenance of retinal tissue homeostasis and the preservation of cone integrity. It also suggests that YAP haploinsufficiency should be considered and explored as a cause of cone dystrophies in human. mRNA level relative to control kDA 25 AQP4 Kir4.1 37 50 8 Mo 12 Mo Control Yap +/-Yap +/-Control α-Tub GS GS B 0.0 0.5 1.0 1.5 * Control Yap CKO YAP level of expression (relative to control)

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Section: Compensatory Taz Regulation In Yap +/Post-natal Micesupporting

confidence: 85%

Yaphaploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy

Masson

García-García

Bitard

et al. 2020

Preprint

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“…Appearance or disappearance of transcription factors will alter its choice of cooperation partners and remove or add either antagonistic or synergistic influences. Stage‐specific changes in the regulatory network composition are likely also responsible for the multiple effects of the Hippo signaling components Yap and Taz on Schwann cell development in combination with Tead transcription factors, in particular Tead1, as their nuclear effectors (Deng et al, ; Grove et al, ; Lopez‐Anido et al, ; Poitelon et al, ).…”

Section: Transcriptional Control Of Peripheral Myelination By Lineagementioning

confidence: 99%

“…Stage-specific changes in the regulatory network composition are likely also responsible for the multiple effects of the Hippo signaling components Yap and Taz on Schwann cell development in combination with Tead transcription factors, in particular Tead1, as their nuclear effectors (Deng et al, 2017;Grove et al, 2017;Lopez-Anido et al, 2016;Poitelon et al, 2016).…”

Section: Transcriptional Control Of Peripheral Myelination By Lineamentioning

confidence: 99%

Transcriptional control of myelination and remyelination

Sock

Wegner

2019

Glia

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Myelination is an evolutionary recent differentiation program that has been independently acquired in vertebrates by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. Therefore, it is not surprising that regulating transcription factors differ substantially between both cell types. However, overall principles are similar as transcriptional control in Schwann cells and oligodendrocytes combines lineage determining and stage‐specific factors in complex regulatory networks. Myelination does not only occur during development, but also as remyelination in the adult. In line with the different conditions during developmental myelination and remyelination and the distinctive properties of Schwann cells and oligodendrocytes, transcriptional regulation of remyelination exhibits unique features and differs between the two cell types. This review gives an overview of the current state in the field.

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“…The mammalian adaptive immune system is also influenced by the activation of the Hippo signaling pathway (Yamauchi & Moroishi, ). Even during the development of the nervous system, the Hippo pathway is responsible for the proliferation of neuronal progenitors (Cao, Pfaff, & Gage, ), their differentiation (Lin et al, ), migration (Fry et al, ), myelination (Deng et al, ), dendritic arborization (Emoto, ), and successful neural connectivity formation (Sakuma et al, ). Although less explored, the Hippo signaling pathway is getting a lot of attention in recent days for its latent biological importance.…”

Section: Biological Functions Of the Hippo Signaling Pathwaymentioning

confidence: 99%

The emerging role of Hippo signaling in neurodegeneration

Sahu

Mondal

2019

J of Neuroscience Research

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Neurodegeneration refers to the complex process of progressive degeneration or neuronal apoptosis leading to a set of incurable and debilitating conditions. Physiologically, apoptosis is important in proper growth and development. However, aberrant and unrestricted apoptosis can lead to a variety of degenerative conditions including neurodegenerative diseases. Although dysregulated apoptosis has been implicated in various neurodegenerative disorders, the triggers and molecular mechanisms underlying such untimely and faulty apoptosis are still unknown. Hippo signaling pathway is one such apoptosis‐regulating mechanism that has remained evolutionarily conserved from Drosophila to mammals. This pathway has gained a lot of attention for its tumor‐suppressing task, but recent studies have emphasized the soaring role of this pathway in inflaming neurodegeneration. In addition, strategies promoting inactivation of this pathway have aided in the rescue of neurons from anomalous apoptosis. So, a thorough understanding of the relationship between the Hippo pathway and neurodegeneration may serve as a guide for the development of therapy for various degenerative diseases. The current review focuses on the mechanism of the Hippo signaling pathway, its upstream and downstream regulatory molecules, and its role in the genesis of numerous neurodegenerative diseases. The recent efforts employing the Hippo pathway components as targets for checking neurodegeneration have also been highlighted.

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A reciprocal regulatory loop between TAZ/YAP and G-protein Gαs regulates Schwann cell proliferation and myelination

Cited by 78 publications

References 65 publications

Yaphaploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy

Yaphaploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy

Transcriptional control of myelination and remyelination

The emerging role of Hippo signaling in neurodegeneration

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