The Salvador-Warts-Hippo Pathway Is Required for Epithelial Proliferation and Axis Specification in Drosophila

Meignin, Carine; Alvarez-Garcia, Ines; Davis, Ilan; Palacios, Isabel M.

doi:10.1016/j.cub.2007.09.062

Cited by 96 publications

(132 citation statements)

References 38 publications

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“…Eya should be detected only in follicle cell precursors and main-body follicle cells, but not in polar cells (Bai and Montell 2002). It is possible that the Hippo pathway controls eya expression because ectopic Eya is also detected in posterior follicle cells mutant for hpo or wts after stage 8 (Meignin et al 2007;Polesello and Tapon 2007;Yu et al 2008). Although knockdown of wts or overexpression of yki-3SA increased polar cells, these polar cells did not induce stat-GFP in neighboring cells (Figure 5,C and D).…”

Section: Discussionmentioning

confidence: 95%

The Hippo Pathway Controls Border Cell Migration Through Distinct Mechanisms in Outer Border Cells and Polar Cells of the Drosophila Ovary

Lin¹,

Yeh²,

Wang

et al. 2014

Genetics

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The Hippo pathway is a key signaling cascade in controlling organ size. The core components of this pathway are two kinases, Hippo (Hpo) and Warts (Wts), and a transcriptional coactivator, Yorkie (Yki). Yes-associated protein (YAP, a Yki homolog in mammals) promotes epithelial-mesenchymal transition and cell migration in vitro. Here, we use border cells in the Drosophila ovary as a model to study Hippo pathway functions in cell migration in vivo. During oogenesis, polar cells secrete Unpaired (Upd), which activates JAK/STAT signaling of neighboring cells and specifies them into outer border cells. The outer border cells form a cluster with polar cells and undergo migration. We find that hpo and wts are required for migration of the border cell cluster. In outer border cells, overexpression of hpo disrupts polarization of the actin cytoskeleton and attenuates migration. In polar cells, knockdown of hpo and wts or overexpression of yki impairs border cell induction and disrupts migration. These manipulations in polar cells reduce JAK/STAT activity in outer border cells. Expression of upd-lacZ is increased and decreased in yki and hpo mutant polar cells, respectively. Furthermore, forced expression of upd in polar cells rescues defects of border cell induction and migration caused by wts knockdown. These results suggest that Yki negatively regulates border cell induction by inhibiting JAK/STAT signaling. Together, our data elucidate two distinct mechanisms of the Hippo pathway in controlling border cell migration: (1) in outer border cells, it regulates polarized distribution of the actin cytoskeleton; (2) in polar cells, it regulates upd expression to control border cell induction and migration.

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Section: Discussionmentioning

confidence: 95%

The Hippo Pathway Controls Border Cell Migration Through Distinct Mechanisms in Outer Border Cells and Polar Cells of the Drosophila Ovary

Lin¹,

Yeh²,

Wang

et al. 2014

Genetics

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“…Genetic studies clearly indicate that Fat regulates the Hippo pathway 31, 61-64 , but these and other studies also suggest that there are other, as yet unidentified cell surface receptors [65][66][67] . How the Hippo pathway connects to the Fat and Dachsous cadherins and other cell surface receptors is still unclear and is a point of much current research.…”

Section: Growth Control By Fat Pcp Regulatorsmentioning

confidence: 96%

When pathways collide: collaboration and connivance among signalling proteins in development

McNeill

Woodgett

2010

Nat Rev Mol Cell Biol

141

106

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Signal transduction pathways interact at various levels in defining tissue morphology, size and differentiation during development. Understanding of the mechanisms by which these pathways collude has been greatly enhanced by recent insights into how shared components are independently regulated and how the activity of one system is contextualized by others. Traditionally, the components of signalling pathways have been assumed to show pathway fidelity and to act with a high degree of autonomy. However, as illustrated by the Wnt and Hippo pathways, there is increasing evidence that components are often shared between multiple pathways and other components talk to each other through multiple mechanisms.

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“…6A). Abnormal SWH signaling pathway has been associated with tumorigenesis in both mammalian cells and Drosophila (26,27), and RassF1A is a SWH pathway component controlling cellular proliferation, survival, antiapoptosis, organ size, and cell contact inhibition (20,28). Because loss of function of these 9 genes (Fig.…”

Section: Expression Of Stem Cell Markers In Me_handr Mscderived Tumorsmentioning

confidence: 99%

Targeted Methylation of Two Tumor Suppressor Genes Is Sufficient to Transform Mesenchymal Stem Cells into Cancer Stem/Initiating Cells

et al. 2011

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Although DNA hypermethylation within promoter CpG islands is highly correlated with tumorigenesis, it has not been established whether DNA hypermethylation within a specific tumor suppressor gene (TSG) is sufficient to fully transform a somatic stem cell. In this study, we addressed this question using a novel targeted DNA methylation technique to methylate the promoters of HIC1 and RassF1A, two well-established TSGs, along with a two-component reporter system to visualize successful targeting of human bone marrow-derived mesenchymal stem cells (MSC) as a model cell system. MSCs harboring targeted promoter methylations of HIC1/RassF1A displayed several features of cancer stem/initiating cells including loss of anchorage dependence, increased colony formation capability, drug resistance, and pluripotency. Notably, inoculation of immunodeficient mice with low numbers of targeted MSC resulted in tumor formation, and subsequent serial xenotransplantation and immunohistochemistry confirmed the presence of stem cell markers and MSC lineage in tumor xenografts. Consistent with the expected mechanism of TSG hypermethylation, treatment of the targeted MSC with a DNA methyltransferase inhibitor reversed their tumorigenic phenotype. To our knowledge, this is the first direct demonstration that aberrant TSG hypermethylation is sufficient to transform a somatic stem cell into a fully malignant cell with cancer stem/initiating properties. Cancer Res; 71(13); 4653-63. Ó2011 AACR.

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The Salvador-Warts-Hippo Pathway Is Required for Epithelial Proliferation and Axis Specification in Drosophila

Cited by 96 publications

References 38 publications

The Hippo Pathway Controls Border Cell Migration Through Distinct Mechanisms in Outer Border Cells and Polar Cells of the Drosophila Ovary

The Hippo Pathway Controls Border Cell Migration Through Distinct Mechanisms in Outer Border Cells and Polar Cells of the Drosophila Ovary

When pathways collide: collaboration and connivance among signalling proteins in development

Targeted Methylation of Two Tumor Suppressor Genes Is Sufficient to Transform Mesenchymal Stem Cells into Cancer Stem/Initiating Cells

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