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  1. Article ; Online: Live imaging of the

    Wilcockson, Scott G / Ashe, Hilary L

    STAR protocols

    2021  Volume 2, Issue 1, Page(s) 100371

    Abstract: The maintenance of stem cell populations and the differentiation of their progeny is coordinated by specific communication with associated niche cells. Here, we describe a protocol for short-term live imaging of ... ...

    Abstract The maintenance of stem cell populations and the differentiation of their progeny is coordinated by specific communication with associated niche cells. Here, we describe a protocol for short-term live imaging of the
    MeSH term(s) Adult Germline Stem Cells/cytology ; Animals ; Cell Differentiation ; Drosophila/cytology ; Female ; Germ Cells/cytology ; Molecular Imaging/methods ; Oogonial Stem Cells/cytology ; Ovary/cytology ; Stem Cell Niche/physiology ; Stem Cells/cytology
    Language English
    Publishing date 2021-03-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2021.100371
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Context-dependent TGFβ family signalling in cell fate regulation.

    Richardson, Louise / Wilcockson, Scott G / Guglielmi, Luca / Hill, Caroline S

    Nature reviews. Molecular cell biology

    2023  Volume 24, Issue 12, Page(s) 876–894

    Abstract: The transforming growth factor-β (TGFβ) family are a large group of evolutionarily conserved cytokines whose signalling modulates cell fate decision-making across varying cellular contexts at different stages of life. Here we discuss new findings in ... ...

    Abstract The transforming growth factor-β (TGFβ) family are a large group of evolutionarily conserved cytokines whose signalling modulates cell fate decision-making across varying cellular contexts at different stages of life. Here we discuss new findings in early embryos that reveal how, in contrast to our original understanding of morphogen interpretation, robust cell fate specification can originate from a noisy combination of signalling inputs and a broad range of signalling levels. We compare this evidence with novel findings on the roles of TGFβ family signalling in tissue maintenance and homeostasis during juvenile and adult life, spanning the skeletal, haemopoietic and immune systems. From these comparisons, it emerges that in contrast to robust developing systems, relatively small perturbations in TGFβ family signalling have detrimental effects at later stages in life, leading to aberrant cell fate specification and disease, for example in cancer or congenital disorders. Finally, we highlight novel strategies to target and amend dysfunction in signalling and discuss how gleaning knowledge from different fields of biology can help in the development of therapeutics for aberrant TGFβ family signalling in disease.
    MeSH term(s) Humans ; Transforming Growth Factor beta ; Signal Transduction/physiology ; Neoplasms
    Chemical Substances Transforming Growth Factor beta
    Language English
    Publishing date 2023-08-18
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/s41580-023-00638-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: An improved Erk biosensor detects oscillatory Erk dynamics driven by mitotic erasure during early development.

    Wilcockson, Scott G / Guglielmi, Luca / Araguas Rodriguez, Pablo / Amoyel, Marc / Hill, Caroline S

    Developmental cell

    2023  Volume 58, Issue 23, Page(s) 2802–2818.e5

    Abstract: Extracellular signal-regulated kinase (Erk) signaling dynamics elicit distinct cellular responses in a variety of contexts. The early zebrafish embryo is an ideal model to explore the role of Erk signaling dynamics in vivo, as a gradient of activated ... ...

    Abstract Extracellular signal-regulated kinase (Erk) signaling dynamics elicit distinct cellular responses in a variety of contexts. The early zebrafish embryo is an ideal model to explore the role of Erk signaling dynamics in vivo, as a gradient of activated diphosphorylated Erk (P-Erk) is induced by fibroblast growth factor (Fgf) signaling at the blastula margin. Here, we describe an improved Erk-specific biosensor, which we term modified Erk kinase translocation reporter (modErk-KTR). We demonstrate the utility of this biosensor in vitro and in developing zebrafish and Drosophila embryos. Moreover, we show that Fgf/Erk signaling is dynamic and coupled to tissue growth during both early zebrafish and Drosophila development. Erk activity is rapidly extinguished just prior to mitosis, which we refer to as mitotic erasure, inducing periods of inactivity, thus providing a source of heterogeneity in an asynchronously dividing tissue. Our modified reporter and transgenic lines represent an important resource for interrogating the role of Erk signaling dynamics in vivo.
    MeSH term(s) Animals ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Zebrafish/metabolism ; Signal Transduction ; Fibroblast Growth Factors/metabolism ; Drosophila/metabolism ; Biosensing Techniques
    Chemical Substances Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Fibroblast Growth Factors (62031-54-3)
    Language English
    Publishing date 2023-09-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2023.08.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Drosophila Ovarian Germline Stem Cell Cytocensor Projections Dynamically Receive and Attenuate BMP Signaling.

    Wilcockson, Scott G / Ashe, Hilary L

    Developmental cell

    2019  Volume 50, Issue 3, Page(s) 296–312.e5

    Abstract: In the Drosophila ovarian germline, Bone Morphogenetic Protein (BMP) signals released by niche cells promote germline stem cell (GSC) maintenance. Although BMP signaling is known to repress expression of a key differentiation factor, it remains unclear ... ...

    Abstract In the Drosophila ovarian germline, Bone Morphogenetic Protein (BMP) signals released by niche cells promote germline stem cell (GSC) maintenance. Although BMP signaling is known to repress expression of a key differentiation factor, it remains unclear whether BMP-responsive transcription also contributes positively to GSC identity. Here, we identify the GSC transcriptome using RNA sequencing (RNA-seq), including the BMP-induced transcriptional network. Based on these data, we provide evidence that GSCs form two types of cellular projections. Genetic manipulation and live ex vivo imaging reveal that both classes of projection allow GSCs to access a reservoir of Dpp held away from the GSC-niche interface. Moreover, microtubule-rich projections, termed "cytocensors", form downstream of BMP and have additional functionality, which is to attenuate BMP signaling. In this way, cytocensors allow dynamic modulation of signal transduction to facilitate differentiation following GSC division. This ability of cytocensors to attenuate the signaling response expands the repertoire of functions associated with signaling projections.
    MeSH term(s) Animals ; Bone Morphogenetic Proteins/genetics ; Bone Morphogenetic Proteins/metabolism ; Cell Differentiation ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster ; Female ; Gene Expression Regulation, Developmental ; Ovary/cytology ; Signal Transduction ; Stem Cell Niche ; Stem Cells/cytology ; Stem Cells/metabolism
    Chemical Substances Bone Morphogenetic Proteins ; Drosophila Proteins ; dpp protein, Drosophila
    Language English
    Publishing date 2019-06-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2019.05.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Live imaging of the Drosophila ovarian germline stem cell niche

    Scott G. Wilcockson / Hilary L. Ashe

    STAR Protocols, Vol 2, Iss 1, Pp 100371- (2021)

    2021  

    Abstract: ... of this protocol, please refer to Wilcockson and Ashe (2019). ...

    Abstract Summary: The maintenance of stem cell populations and the differentiation of their progeny is coordinated by specific communication with associated niche cells. Here, we describe a protocol for short-term live imaging of the Drosophila ovarian germline stem cell niche ex vivo. By immobilizing the ovarian tissue in a fibrinogen-thrombin clot, we are able to maintain the tissue for short-term high-temporal live imaging. This enables the visualization of dynamic cellular processes, such as the cytoskeletal dynamics that control stem cell niche communication.For complete details on the use and execution of this protocol, please refer to Wilcockson and Ashe (2019).
    Keywords Cell Biology ; Microscopy ; Model Organisms ; Stem Cells ; Science (General) ; Q1-390
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Control of signaling molecule range during developmental patterning

    Wilcockson, Scott G / Catherine Sutcliffe / Hilary L. Ashe

    Cellular and molecular life sciences. 2017 June, v. 74, no. 11

    2017  

    Abstract: Tissue patterning, through the concerted activity of a small number of signaling pathways, is critical to embryonic development. While patterning can involve signaling between neighbouring cells, in other contexts signals act over greater distances by ... ...

    Abstract Tissue patterning, through the concerted activity of a small number of signaling pathways, is critical to embryonic development. While patterning can involve signaling between neighbouring cells, in other contexts signals act over greater distances by traversing complex cellular landscapes to instruct the fate of distant cells. In this review, we explore different strategies adopted by cells to modulate signaling molecule range to allow correct patterning. We describe mechanisms for restricting signaling range and highlight how such short-range signaling can be exploited to not only control the fate of adjacent cells, but also to generate graded signaling within a field of cells. Other strategies include modulation of signaling molecule action by tissue architectural properties and the use of cellular membranous structures, such as signaling filopodia and exosomes, to actively deliver signaling ligands to target cells. Signaling filopodia can also be deployed to reach out and collect particular signals, thereby precisely controlling their site of action.
    Keywords embryogenesis ; exosomes ; landscapes ; ligands ; pseudopodia ; signal transduction
    Language English
    Dates of publication 2017-06
    Size p. 1937-1956.
    Publishing place Springer International Publishing
    Document type Article
    Note Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-016-2433-5
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Control of signaling molecule range during developmental patterning.

    Wilcockson, Scott G / Sutcliffe, Catherine / Ashe, Hilary L

    Cellular and molecular life sciences : CMLS

    2016  Volume 74, Issue 11, Page(s) 1937–1956

    Abstract: Tissue patterning, through the concerted activity of a small number of signaling pathways, is critical to embryonic development. While patterning can involve signaling between neighbouring cells, in other contexts signals act over greater distances by ... ...

    Abstract Tissue patterning, through the concerted activity of a small number of signaling pathways, is critical to embryonic development. While patterning can involve signaling between neighbouring cells, in other contexts signals act over greater distances by traversing complex cellular landscapes to instruct the fate of distant cells. In this review, we explore different strategies adopted by cells to modulate signaling molecule range to allow correct patterning. We describe mechanisms for restricting signaling range and highlight how such short-range signaling can be exploited to not only control the fate of adjacent cells, but also to generate graded signaling within a field of cells. Other strategies include modulation of signaling molecule action by tissue architectural properties and the use of cellular membranous structures, such as signaling filopodia and exosomes, to actively deliver signaling ligands to target cells. Signaling filopodia can also be deployed to reach out and collect particular signals, thereby precisely controlling their site of action.
    MeSH term(s) Animals ; Body Patterning ; Cell Surface Extensions/metabolism ; Embryonic Development ; Extracellular Vesicles/metabolism ; Humans ; Ligands ; Signal Transduction
    Chemical Substances Ligands
    Language English
    Publishing date 2016-12-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-016-2433-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Peak BMP Responses in the Drosophila Embryo Are Dependent on the Activation of Integrin Signaling.

    Sawala, Annick / Scarcia, Margherita / Sutcliffe, Catherine / Wilcockson, Scott G / Ashe, Hilary L

    Cell reports

    2015  Volume 13, Issue 7, Page(s) 1519–1520

    Language English
    Publishing date 2015-11-17
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2015.10.079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Peak BMP Responses in the Drosophila Embryo Are Dependent on the Activation of Integrin Signaling.

    Sawala, Annick / Scarcia, Margherita / Sutcliffe, Catherine / Wilcockson, Scott G / Ashe, Hilary L

    Cell reports

    2015  Volume 12, Issue 10, Page(s) 1584–1593

    Abstract: Within a 3D tissue, cells need to integrate signals from growth factors, such as BMPs, and the extracellular matrix (ECM) to coordinate growth and differentiation. Here, we use the Drosophila embryo as a model to investigate how BMP responses are ... ...

    Abstract Within a 3D tissue, cells need to integrate signals from growth factors, such as BMPs, and the extracellular matrix (ECM) to coordinate growth and differentiation. Here, we use the Drosophila embryo as a model to investigate how BMP responses are influenced by a cell's local ECM environment. We show that integrins, which are ECM receptors, are absolutely required for peak BMP signaling. This stimulatory effect of integrins requires their intracellular signaling function, which is activated by the ECM protein collagen IV. Mechanistically, integrins interact with the BMP receptor and stimulate phosphorylation of the downstream Mad transcription factor. The BMP-pathway-enhancing function of integrins is independent of focal adhesion kinase, but it requires conserved NPXY motifs in the β-integrin cytoplasmic tail. Furthermore, we show that an α-integrin subunit is a BMP target gene, identifying positive feedback between integrin signaling and BMP pathway activity that may contribute to robust cell fate decisions.
    MeSH term(s) Animals ; Bone Morphogenetic Proteins/physiology ; Cell Line ; Collagen Type IV/genetics ; Collagen Type IV/metabolism ; Drosophila Proteins/physiology ; Drosophila melanogaster/embryology ; Drosophila melanogaster/metabolism ; Embryo, Nonmammalian/metabolism ; Embryonic Development ; Feedback, Physiological ; Gene Expression ; Gene Expression Regulation, Developmental ; Integrins/physiology ; Signal Transduction
    Chemical Substances Bone Morphogenetic Proteins ; Collagen Type IV ; Drosophila Proteins ; Integrins
    Language English
    Publishing date 2015-09-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2015.08.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Pupil dilation reflects the authenticity of received nonverbal vocalizations.

    Cosme, Gonçalo / Rosa, Pedro J / Lima, César F / Tavares, Vânia / Scott, Sophie / Chen, Sinead / Wilcockson, Thomas D W / Crawford, Trevor J / Prata, Diana

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 3733

    Abstract: The ability to infer the authenticity of other's emotional expressions is a social cognitive process taking place in all human interactions. Although the neurocognitive correlates of authenticity recognition have been probed, its potential recruitment of ...

    Abstract The ability to infer the authenticity of other's emotional expressions is a social cognitive process taking place in all human interactions. Although the neurocognitive correlates of authenticity recognition have been probed, its potential recruitment of the peripheral autonomic nervous system is not known. In this work, we asked participants to rate the authenticity of authentic and acted laughs and cries, while simultaneously recording their pupil size, taken as proxy of cognitive effort and arousal. We report, for the first time, that acted laughs elicited higher pupil dilation than authentic ones and, reversely, authentic cries elicited higher pupil dilation than acted ones. We tentatively suggest the lack of authenticity in others' laughs elicits increased pupil dilation through demanding higher cognitive effort; and that, reversely, authenticity in cries increases pupil dilation, through eliciting higher emotional arousal. We also show authentic vocalizations and laughs (i.e. main effects of authenticity and emotion) to be perceived as more authentic, arousing and contagious than acted vocalizations and cries, respectively. In conclusion, we show new evidence that the recognition of emotional authenticity can be manifested at the level of the autonomic nervous system in humans. Notwithstanding, given its novelty, further independent research is warranted to ascertain its psychological meaning.
    Language English
    Publishing date 2021-02-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-83070-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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