The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis

Hamaratoǧlu, Fisun; Willecke, Maria; Kango‐Singh, Madhuri; Nolo, Riitta; Hyun, Eric; Tao, Chunyao; Jafar‐Nejad, Hamed; Halder, Georg

doi:10.1038/ncb1339

Cited by 692 publications

(827 citation statements)

References 46 publications

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“…Since the Egfr ligand acts as a morphogen providing the positional information along the PD axis in the leg imaginal disc, some relation between EGF and the Ds-Ft signaling pathway may exist. This speculation has been supported by studies on tumorigenesis by Hamaratoglu et al (2006).…”

Section: Relationship Between Morphogen Gradients and The Ds-ft Signamentioning

confidence: 67%

“…Mer, the protein product of the Neurofibromatosis type-2 (NF2), acts as a tumor suppressor in mice and humans (Hamaratoglu et al, 2006). Mer is an adaptor protein with a FERM domain.…”

Section: Relationship Between Morphogen Gradients and The Ds-ft Signamentioning

confidence: 99%

“…Mer is an adaptor protein with a FERM domain. In Drosophila, it functions with Ex (Hamaratoglu et al, 2006). Hamaratoglu et al (2006) showed that Drosophila Mer and Ex are required for proliferation arrest and apoptosis in developing imaginal discs and components of the Wts-Hpo signaling pathway.…”

Section: Relationship Between Morphogen Gradients and The Ds-ft Signamentioning

confidence: 99%

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Regulation of leg size and shape: Involvement of the Dachsous‐fat signaling pathway

Bando

Mito

Nakamura

et al. 2011

Developmental Dynamics

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How limb size and shape is regulated is a long-standing question in developmental and regeneration biology. Recently, the protocadherin Dachsous-Fat (Ds-Ft) signaling pathway has been found to be essential for wing development of the fly and leg regeneration of the cricket. The Ds-Ft signaling pathway is linked to the Warts-Hippo (Wts-Hpo) signaling pathway, leading to cell proliferation. Several lines of evidence have suggested that the Wts-Hpo signaling pathway is involved in the control of organ size, and that this pathway is regulated by Ds-Ft and Merlin-Expanded, which are linked to morphogens such as decapentaplegic/bone morphogenic protein, Wingless/Wnt, and epidermal growth factor. Here we review recent progress in elucidating mechanisms controlling leg size and shape in insects and vertebrates, focusing on the Ds-Ft signaling pathway. We also introduce a working model, Ds-Ft steepness model, to explain how steepness of the Ds-Ft gradient controls leg size along the proximodistal axis. Developmental Dynamics 240:1028-1041,

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Section: Relationship Between Morphogen Gradients and The Ds-ft Signamentioning

confidence: 67%

“…Mer, the protein product of the Neurofibromatosis type-2 (NF2), acts as a tumor suppressor in mice and humans (Hamaratoglu et al, 2006). Mer is an adaptor protein with a FERM domain.…”

Section: Relationship Between Morphogen Gradients and The Ds-ft Signamentioning

confidence: 99%

Section: Relationship Between Morphogen Gradients and The Ds-ft Signamentioning

confidence: 99%

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Regulation of leg size and shape: Involvement of the Dachsous‐fat signaling pathway

Bando

Mito

Nakamura

et al. 2011

Developmental Dynamics

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“…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. Some studies suggest that Fat regulates Hippo activity via the FERM domain protein Expanded, which functions redundantly with another FERM domain protein Merlin/NF2 to control Hippo activity 68 . Transcription of fat, dachsous, four-jointed, expanded and merlin are enhanced by loss of Hippo pathway activity, providing negative feedback, and also allowing changes in Hippo activity to be transmitted to adjacent cells.…”

Section: Growth Control By Fat Pcp Regulatorsmentioning

confidence: 99%

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

McNeill

Woodgett

2010

Nat Rev Mol Cell Biol

143

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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“…Other genes found to be involved are members of the Salvador-warts-hippo (SWH) network of proteins (Meignin et al, 2007;Polesello and Tapon, 2007;Udan et al, 2003), the tumor suppressor Merlin/Neurofibromin 2 (mer) (Hamaratoglu et al, 2006;LaJeunesse et al, 1998) and Warts (wts) (MacDougall et al, 2001). These genes are also required at wild-type levels for efficient oocyte destruction.…”

Section: Ssrna Induces Egg Chamber Destructionmentioning

confidence: 99%

Oocyte destruction is activated during viral infection

Thomson

Schneemann

Johnson

2012

Genesis

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Summary: Viral infection has been associated with a starvation-like state in Drosophila melanogaster. Because starvation and inhibiting TOR kinase activity in vivo result in blocked oocyte production, we hypothesized that viral infection would also result in compromised oogenesis. Wild-type flies were injected with flock house virus (FHV) and survival and embryo production were monitored. Infected flies had a doseresponsive loss of fecundity that corresponded to a global reduction in Akt/TOR signaling. Highly penetrant egg chamber destruction mid-way through oogenesis was noted and FHV coat protein was detected within developing egg chambers. As seen with in vivo TOR inhibition, oogenesis was partially rescued in loss of function discs large and merlin mutants. As expected, mutants in genes known to be involved in virus internalization and trafficking [Clathrin heavy chain (chc) and synaptotagmin] survive longer during infection. However, oogenesis was rescued only in chc mutants. This suggests that viral response mechanisms that control fly survival and egg chamber survival are separable. The genetic and signaling requirements for oocyte destruction delineated here represent a novel host-virus interaction with implications for the control of both fly and virus populations. genesis 50:453-465, 2012. V V C 2011 Wiley Periodicals, Inc.

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The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis

Cited by 692 publications

References 46 publications

Regulation of leg size and shape: Involvement of the Dachsous‐fat signaling pathway

Regulation of leg size and shape: Involvement of the Dachsous‐fat signaling pathway

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

Oocyte destruction is activated during viral infection

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