2018
DOI: 10.1371/journal.pbio.2002399
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Hippo signaling controls cell cycle and restricts cell plasticity in planarians

Abstract: The Hippo pathway plays a key role in regulating cell turnover in adult tissues, and abnormalities in this pathway are consistently associated with human cancers. Hippo was initially implicated in the control of cell proliferation and death, and its inhibition is linked to the expansion of stem cells and progenitors, leading to larger organ size and tumor formation. To understand the mechanism by which Hippo directs cell renewal and promotes stemness, we studied its function in planarians. These stem cell–base… Show more

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Cited by 37 publications
(40 citation statements)
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“…This finding appears to contradict the reported role of yki in other regenerative contexts; in both zebrafish and mice hippo inhibition (which induces Yki phosphorylation and nuclearization) activates the regenerative response (Zhou et al, 2015;Loforese et al, 2016). However, we recently found that hippo inhibition (i.e., Yki activation) in planarians promotes cell plasticity and acquisition of stemness (de Sousa et al, 2018). While this effect does not promote a regenerative response, it is in agreement with the reported role of Yki as a stemness promoter in other models (Pfleger, 2017).…”
Section: Size Control and Organ Proportionalitymentioning
confidence: 77%
“…This finding appears to contradict the reported role of yki in other regenerative contexts; in both zebrafish and mice hippo inhibition (which induces Yki phosphorylation and nuclearization) activates the regenerative response (Zhou et al, 2015;Loforese et al, 2016). However, we recently found that hippo inhibition (i.e., Yki activation) in planarians promotes cell plasticity and acquisition of stemness (de Sousa et al, 2018). While this effect does not promote a regenerative response, it is in agreement with the reported role of Yki as a stemness promoter in other models (Pfleger, 2017).…”
Section: Size Control and Organ Proportionalitymentioning
confidence: 77%
“…5G). Recent research demonstrates the intriguing possibility that inhibition of Hippo signaling trigger dedifferentiation of postmitotic progenitors in pla- narians [142]. It is tantalizing to speculate that the increasing load of genomic instability may act as a switch for zeta nebolasts to leave their lineage-restricted state and try to fill the niche left behind by sigma cells that cannot survive increasing DNA damage.…”
Section: Functional Disruption Of Rad51 and Ubc9 Affects Tissue Homeomentioning
confidence: 99%
“…Cellular studies demonstrated that the underlying mechanism of overgrowth formation was not an increase in cell proliferation but in arresting the cell cycle, inhibiting apoptosis and promoting cell dedifferentiation [19]. Due to the complex phenotype obtained, the functional study of yorkie did not allow to relate it with the Hippo function [19] [20]. Here, we show that inhibition of the core kinase elements salvador and warts promotes the appearance of undifferentiated regions and overgrowths, phenocopying the hippo RNAi phenotype.…”
Section: Introductionmentioning
confidence: 83%
“…This continuous active regulation of the stem cell and postmitotic cell compartments makes the planarian an ideal in vivo model to understand the mechanisms underlying homeostatic cell renewal [17] [18]. It was recently shown that inhibition of hippo in planarians promoted the appearance of undifferentiated regions and overgrowths [19]. Cellular studies demonstrated that the underlying mechanism of overgrowth formation was not an increase in cell proliferation but in arresting the cell cycle, inhibiting apoptosis and promoting cell dedifferentiation [19].…”
Section: Introductionmentioning
confidence: 99%
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