YAP controls retinal stem cell DNA replication timing and genomic stability

Cabochette, Pauline; Vega-Lopez, Guillermo A.; Bitard, Juliette; Parain, Karine; Chemouny, Romain; Masson, Christel; Borday, Caroline; Hedderich, Marie; Henningfeld, Kristine A.; Locker, Morgane; Bronchain, Odile; Perron, Muriel

doi:10.7554/elife.08488

Cited by 45 publications

(66 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proneural bHLH transcription factors inhibit Yap by directly inhibiting Yap transcription and by activating upstream kinase Lats1/2. A recent study of frog CMZ stem cells illustrated Yap’s essential role in cell cycle regulation, especially at S phase (Cabochette et al, 2015). Total cell cycle length of Yap -deficient CMZ stem cells was increased while S-phase length was drastically shortened, presumably by skipping replication firing.…”

Section: Discussionmentioning

confidence: 99%

Yap is essential for retinal progenitor cell cycle progression and RPE cell fate acquisition in the developing mouse eye

Kim

Park

Lee

et al. 2016

Developmental Biology

View full text Add to dashboard Cite

Yap functions as a transcriptional regulator by acting together with sequence-specific DNA binding factors and transcription cofactors to mediate cell proliferation in developing epithelial tissues and tumors. An upstream kinase cascade controls nuclear localization and function in response to partially identified exogenous signals, including cell-to-cell contact. Nevertheless, its role in CNS development is poorly understood. In order to investigate Yap function in developing CNS, we characterized the cellular outcomes after selective Yap gene ablation in developing ocular tissues. When Yap was lost, presumptive retinal pigment epithelium acquired anatomical and molecular characteristics resembling those of the retinal epithelium rather than of RPE, including loss of pigmentation, pseudostratified epithelial morphology and ectopic induction of markers for retinal progenitor cells, like Chx10, and neurons, like β-Tubulin III. In addition, developing retina showed signs of progressive degeneration, including laminar folding, thinning and cell loss, which resulted from multiple defects in cell proliferation and survival, and in junction integrity. Furthermore, Yap-deficient retinal progenitors displayed decreased S-phase cells and altered cell cycle progression. Altogether, our studies not only illustrate the canonical function of Yap in promoting the proliferation of progenitors, but also shed new light on its evolutionarily conserved, instructive role in regional specification, maintenance of junctional integrity and precise regulation of cell proliferation during neuroepithelial development.

show abstract

Section: Discussionmentioning

confidence: 99%

Yap is essential for retinal progenitor cell cycle progression and RPE cell fate acquisition in the developing mouse eye

Kim

Park

Lee

et al. 2016

Developmental Biology

View full text Add to dashboard Cite

show abstract

“…LATS1 also interacts with CDK2 in response to genotoxic stress to restrict CDK2-mediated phosphorylation of BRCA2 and support RAD51 nucleofilaments, thereby maintaining genome fidelity during replication stalling (Pefani et al 2014). YAP, in complex with the transcription factor PKNOX1, has been shown to control S-phase temporal progression and genomic stability of retinal stem cells (Cabochette et al 2015).…”

Section: Cell Cyclementioning

confidence: 99%

Mechanisms of Hippo pathway regulation

2016

View full text Add to dashboard Cite

The Hippo pathway was initially identified in Drosophila melanogaster screens for tissue growth two decades ago and has been a subject extensively studied in both Drosophila and mammals in the last several years. The core of the Hippo pathway consists of a kinase cascade, transcription coactivators, and DNA-binding partners. Recent studies have expanded the Hippo pathway as a complex signaling network with >30 components. This pathway is regulated by intrinsic cell machineries, such as cell–cell contact, cell polarity, and actin cytoskeleton, as well as a wide range of signals, including cellular energy status, mechanical cues, and hormonal signals that act through G-protein-coupled receptors. The major functions of the Hippo pathway have been defined to restrict tissue growth in adults and modulate cell proliferation, differentiation, and migration in developing organs. Furthermore, dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. In this review, we focus on recent developments in our understanding of the molecular actions of the core Hippo kinase cascade and discuss key open questions in the regulation and function of the Hippo pathway.

show abstract

“…Retinal regeneration also occurs in fish and chick, but not in humans, where retinal degeneration is a major health problem in ageing populations. Muriel Perron (University Paris-Saclay, France) showed that both CMZ and Müller glial cells regenerate the retina in Xenopus, where the Hippo pathway effector YAP regulates S-phase progression of CMZ retinal stem cells (Cabochette et al, 2015). In mouse Müller cells, YAP appears to control the balance between the beneficial and detrimental effects of glial reactivation, positively regulating cell cycle genes and neurotrophic factors, and negatively controlling gliosis genes that prevent retina regeneration in mammals.…”

Section: Regeneration Of the Cnsmentioning

confidence: 99%

Trends in tissue repair and regeneration

et al. 2017

View full text Add to dashboard Cite

The 6th EMBO conference on the Molecular and Cellular Basis of Regeneration and Tissue Repair took place in Paestum (Italy) on the 17th-21st September, 2016. The 160 scientists who attended discussed the importance of cellular and tissue plasticity, biophysical aspects of regeneration, the diverse roles of injury-induced immune responses, strategies to reactivate regeneration in mammals, links between regeneration and ageing, and the impact of non-mammalian models on regenerative medicine.

show abstract

YAP controls retinal stem cell DNA replication timing and genomic stability

Cited by 45 publications

References 65 publications

Yap is essential for retinal progenitor cell cycle progression and RPE cell fate acquisition in the developing mouse eye

Yap is essential for retinal progenitor cell cycle progression and RPE cell fate acquisition in the developing mouse eye

Mechanisms of Hippo pathway regulation

Trends in tissue repair and regeneration

Contact Info

Product

Resources

About