Genes of Hippo signaling network act unconventionally in the control of germline proliferation in <i>Drosophila</i>

Sun, Shyan; Zhao, Shaowei; Wang, Zhaohui

doi:10.1002/dvdy.21411

Cited by 20 publications

(18 citation statements)

References 31 publications

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“…Clonal mis‐expression of an activated form of Yki (Yki Act (Oh & Irvine, )) resulted in CySC clones that out‐competed wild‐type CySCs and GSCs at the niche (Fig G and H, P < 0.0014). Consistent with an essential role of yki in CySCs, we found that yki was required autonomously for self‐renewal in CySCs but not in GSCs (Fig A, E and F), the latter consistent with a prior report (Sun et al , ). Finally, we addressed whether Hh and Hpo, two proliferative pathways in CySCs, were epistatic.…”

Section: Resultssupporting

confidence: 92%

“…However, careful analysis of GSC dynamics has suggested that they also undergo neutral competition, albeit at a slower loss/replacement rate than CySCs (Wallenfang et al, 2006;Sheng & Matunis, 2011;Salzmann et al, 2013). Thus, within the same stem cell niche, two markedly different strategies for selfrenewal are in use, exemplified by the requirement for yki in CySC self-renewal, but not in GSC self-renewal (this study and Sun et al, 2008). This is particularly surprising as the two stem cell populations are by necessity linked, in that they need to produce offspring in the correct ratio, as well as the fact that CySCs support GSC self-renewal through BMP production (Leatherman & Dinardo, 2010).…”

Section: Discussionmentioning

confidence: 80%

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Neutral competition of stem cells is skewed by proliferative changes downstream of Hh and Hpo

2014

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Neutral competition, an emerging feature of stem cell homeostasis, posits that individual stem cells can be lost and replaced by their neighbors stochastically, resulting in chance dominance of a clone at the niche. A single stem cell with an oncogenic mutation could bias this process and clonally spread the mutation throughout the stem cell pool. The Drosophila testis provides an ideal system for testing this model. The niche supports two stem cell populations that compete for niche occupancy. Here, we show that cyst stem cells (CySCs) conform to the paradigm of neutral competition and that clonal deregulation of either the Hedgehog (Hh) or Hippo (Hpo) pathway allows a single CySC to colonize the niche. We find that the driving force behind such behavior is accelerated proliferation. Our results demonstrate that a single stem cell colonizes its niche through oncogenic mutation by co-opting an underlying homeostatic process.

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 80%

Neutral competition of stem cells is skewed by proliferative changes downstream of Hh and Hpo

2014

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“…This is why the fecundity of BmYki RNAi silkworm was significantly reduced (Liu et al, ). Furthermore, we noticed that the expression of BmYki in TE did not increase in later developmental stages, which is consistent with previous observations that overexpression of BmYki did not lead to spermatogonial proliferation (Sun et al, ). BmYki expression was extremely high in MG, which affects the uptake of nutrients and, indirectly, body size (Fig.…”

Section: Discussionsupporting

confidence: 92%

Genome editing reveals the function of Yorkie during the embryonic and early larval development in silkworm, Bombyx mori

Zhang

Yang

et al. 2018

Insect Molecular Biology

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As a transcriptional coactivator, Yorkie (Yki) is a major downstream target of the Hippo signalling pathway to regulate the organ size during animal development and regeneration. Previous microarray analysis in the silkworm, Bombyx mori, has shown that genes associated with the Hippo pathway were primarily expressed in gonads and imaginal discs. The RNA-interference-mediated silencing of Yki at the early wandering stage delayed B. mori development and ovary maturation, whereas baculovirus-mediated overexpression at the late larval instar facilitated organ growth and accelerated metamorphosis. Here, we employed CRISPR/Cas9-mediated mutagenesis to investigate the function of Yki in B. mori (BmYki) at the embryonic and early larval stages. Knocking out of BmYki led to reduced body size, moulting defects and, eventually, larval lethality. Sequence analysis of CRISPR/Cas9 mutants exhibited an array of deletions in BmYki. As a critical downstream effector of the Hippo kinase cassette, silencing of BmYki at the embryonic stage is indispensable and the consequence is lethal. Given that the Hippo signalling pathway is evolutionarily conserved, Yki has the potential to be a novel molecular target for genetic-based pest management practices.

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“…As one of the most crucial cell signaling pathways, the Hippo signaling pathway regulates female reproductive system development [34,35,36,37,38]. We provide evidence for the expression of Hippo pathway genes in the different stage mouse ovaries and propose a novel role for Hippo signaling in regulating primordial follicle formation.…”

Section: Discussionmentioning

confidence: 86%

Hippo Signaling Pathway Reveals a Spatio-Temporal Correlation with the Size of Primordial Follicle Pool in Mice

Xiang

et al. 2015

Cell Physiol Biochem

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Background: The Hippo signaling pathway, a highly conserved cell signaling system, exists in most multicellular organisms and regulates cell proliferation, differentiation, and apoptosis. It has been reported that the members of Hippo signaling are expressed in mammalian ovaries, but the exact functions of this pathway in primordial follicle development remains unclear. Methods: To analyze the spatio-temporal correlation between the core component of Hippo pathway and the size of primordial follicle pool, Western blot, Real-time PCR and immunohistochemistry were used, and the expression and localization of MST1, LATS2 and YAP1 mRNA and protein were examined in 3 d, 1 m, 5 m, 16 m postnatal mice ovary and the culture model of mice primordial follicle in vitro. Results: Both the protein and mRNA expression of the MST1 and LATS2 were decreased significantly as mouse age increased (p < 0.05), however, the mRNA expression of them increased significantly in 16 m compared with 5 m as well as the protein expression of LATS2.The expression of YAP showed the opposite trend, and the significant protein expression of pYAP was increased before 1 m, after which no significant change was observed. Moreover, the ratio of pYAP/YAP decreased significantly. Culturing ovaries for 8 d in vitro resulted in the activation of primordial follicles in 3 d postnatal mice ovaries, and these developed into primary follicles with the expression of PCNA increasing significantly (p < 0.05). The mRNA and protein expression of MST and LATS decreased significantly (p < 0.05), and the expression of YAP increased significantly (p < 0.05, p < 0.01), whereas the ratio of pYAP/YAP decreased significantly (p < 0.05). Conclusion: The above results reveal that the expression of the core components of Hippo pathway changed during mouse follicular development, especially before and after primordial follicle activation in vitro. The primordial follicle activation may be related to the significant decrease of the ratio of pYAP1/YAP1. In conclusion, Hippo signaling pathway expressed in mice ovaries and have spatio-temporal correlation with the size of primordial follicle pool.

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Genes of Hippo signaling network act unconventionally in the control of germline proliferation in Drosophila

Cited by 20 publications

References 31 publications

Neutral competition of stem cells is skewed by proliferative changes downstream of Hh and Hpo

Neutral competition of stem cells is skewed by proliferative changes downstream of Hh and Hpo

Genome editing reveals the function of Yorkie during the embryonic and early larval development in silkworm, Bombyx mori

Hippo Signaling Pathway Reveals a Spatio-Temporal Correlation with the Size of Primordial Follicle Pool in Mice

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