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Article ; Online: The extracellular matrix in tissue morphogenesis: No longer a backseat driver.

Díaz-de-la-Loza, María-Del-Carmen / Stramer, Brian M

Cells & development

2023 Volume 177, Page(s) 203883

Abstract: The forces driving tissue morphogenesis are thought to originate from cellular activities. While it is appreciated that extracellular matrix (ECM) may also be involved, ECM function is assumed to be simply instructive in modulating the cellular behaviors ...

Abstract	The forces driving tissue morphogenesis are thought to originate from cellular activities. While it is appreciated that extracellular matrix (ECM) may also be involved, ECM function is assumed to be simply instructive in modulating the cellular behaviors that drive changes to tissue shape. However, there is increasing evidence that the ECM may not be the passive player portrayed in developmental biology textbooks. In this review we highlight examples of embryonic ECM dynamics that suggest cell-independent activity, along with developmental processes during which localized ECM alterations and ECM-autonomous forces are directing changes to tissue shape. Additionally, we discuss experimental approaches to unveil active ECM roles during tissue morphogenesis. We propose that it may be time to rethink our general definition of morphogenesis as a cellular-driven phenomenon and incorporate an underappreciated, and surprisingly dynamic ECM.
MeSH term(s)	Extracellular Matrix ; Morphogenesis
Language	English
Publishing date	2023-11-06
Publishing country	Netherlands
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2667-2901
ISSN (online)	2667-2901
DOI	10.1016/j.cdev.2023.203883
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Article ; Online: Convergent insulin and TGF-β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model.

Bakopoulos, Daniel / Golenkina, Sofya / Dark, Callum / Christie, Elizabeth L / Sánchez-Sánchez, Besaiz J / Stramer, Brian M / Cheng, Louise Y

EMBO reports

2023 Volume 24, Issue 12, Page(s) e57695

Abstract: In this study, we found that in the adipose tissue of wildtype animals, insulin and TGF-β signalling converge via a BMP antagonist short gastrulation (sog) to regulate ECM remodelling. In tumour bearing animals, Sog also modulates TGF-β signalling to ... ...

Abstract	In this study, we found that in the adipose tissue of wildtype animals, insulin and TGF-β signalling converge via a BMP antagonist short gastrulation (sog) to regulate ECM remodelling. In tumour bearing animals, Sog also modulates TGF-β signalling to regulate ECM accumulation in the fat body. TGF-β signalling causes ECM retention in the fat body and subsequently depletes muscles of fat body-derived ECM proteins. Activation of insulin signalling, inhibition of TGF-β signalling, or modulation of ECM levels via SPARC, Rab10 or Collagen IV in the fat body, is able to rescue tissue wasting in the presence of tumour. Together, our study highlights the importance of adipose ECM remodelling in the context of cancer cachexia.
MeSH term(s)	Animals ; Cachexia/etiology ; Cachexia/metabolism ; Drosophila ; Insulin ; Fat Body/metabolism ; Adipose Tissue/metabolism ; Transforming Growth Factor beta ; Neoplasms/complications
Chemical Substances	Insulin ; Transforming Growth Factor beta
Language	English
Publishing date	2023-11-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.202357695
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Article ; Online: A workflow for rapid unbiased quantification of fibrillar feature alignment in biological images.

Marcotti, Stefania / de Freitas, Deandra Belo / Troughton, Lee D / Kenny, Fiona N / Shaw, Tanya J / Stramer, Brian M / Oakes, Patrick W

Frontiers in computer science

2021 Volume 3

Abstract: Measuring the organisation of the cellular cytoskeleton and the surrounding extracellular matrix (ECM) is currently of wide interest as changes in both local and global alignment can highlight alterations in cellular functions and material properties of ... ...

Abstract	Measuring the organisation of the cellular cytoskeleton and the surrounding extracellular matrix (ECM) is currently of wide interest as changes in both local and global alignment can highlight alterations in cellular functions and material properties of the extracellular environment. Different approaches have been developed to quantify these structures, typically based on fibre segmentation or on matrix representation and transformation of the image, each with its own advantages and disadvantages. Here we present
Language	English
Publishing date	2021-10-14
Publishing country	Switzerland
Document type	Journal Article
ISSN	2624-9898
ISSN (online)	2624-9898
DOI	10.3389/fcomp.2021.745831
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Article ; Online: Cells on film - the past and future of cinemicroscopy.

Stramer, Brian M / Dunn, Graham A

Journal of cell science

2014 Volume 128, Issue 1, Page(s) 9–13

Abstract: Movie making is now a ubiquitous experimental tool that biologists use alongside more traditional techniques such as molecular biology and biochemistry. It is no longer just cell biologists, but scientists from many other disciplines, such as immunology ... ...

Abstract	Movie making is now a ubiquitous experimental tool that biologists use alongside more traditional techniques such as molecular biology and biochemistry. It is no longer just cell biologists, but scientists from many other disciplines, such as immunology and neuroscience, that utilise movies to dissect their processes of interest. When did filming become such a standard laboratory technique? Who developed the use of the movie as an experimental tool? The Wellcome Library has recently restored and digitized a number of original 16-mm films from two pioneering cinemicroscopists, Ronald Canti and Michael Abercrombie, which are now freely available to the scientific community. In light of these films, this Essay will give a brief history of the early cinemicroscopists and discuss what is driving the use of movies in the laboratory today.
MeSH term(s)	History, 20th Century ; History, 21st Century ; Microscopy, Video/history ; Microscopy, Video/methods ; Microscopy, Video/trends
Language	English
Publishing date	2014-12-30
Publishing country	England
Document type	Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.165019
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Zs.A 1200: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Unraveling tissue repair immune responses in flies.

Stramer, Brian M / Dionne, Marc S

Seminars in immunology

2014 Volume 26, Issue 4, Page(s) 310–314

Abstract: Drosophila melanogaster has emerged as a powerful model to understand innate immune responses to infection (note the 2011 Nobel Prize in Physiology or Medicine), and in recent years this system has begun to inform on the role and regulation of immune ... ...

Abstract	Drosophila melanogaster has emerged as a powerful model to understand innate immune responses to infection (note the 2011 Nobel Prize in Physiology or Medicine), and in recent years this system has begun to inform on the role and regulation of immune responses during tissue injury. Due to the speed and complexity of inflammation signals upon damage, a complete understanding of the immune responses during repair requires a combination of live imaging at high temporal resolution and genetic dissection, which is possible in a number of different injury models in the fly. Here we discuss the range of wound-induced immune responses that can be modeled in flies. These wound models have revealed the most immediate signals leading to immune cell activation, and highlighted a number of complex signaling cascades required for subsequent injury-associated inflammatory responses. What has emerged from this system are a host of both local acting signals, and surprisingly, more systemic tissue repair immune responses.
MeSH term(s)	Animals ; Drosophila melanogaster/immunology ; Drosophila melanogaster/physiology ; Immunity, Cellular ; Immunity, Humoral ; Inflammation/immunology ; Models, Animal ; Wound Healing
Language	English
Publishing date	2014-05-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1018141-6
ISSN	1096-3618 ; 1044-5323
ISSN (online)	1096-3618
ISSN	1044-5323
DOI	10.1016/j.smim.2014.04.004
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Article ; Online: Extracellular matrix assembly stress initiates Drosophila central nervous system morphogenesis.

Serna-Morales, Eduardo / Sánchez-Sánchez, Besaiz J / Marcotti, Stefania / Nichols, Angus / Bhargava, Anushka / Dragu, Anca / Hirvonen, Liisa M / Díaz-de-la-Loza, María-Del-Carmen / Mink, Matyas / Cox, Susan / Rayfield, Emily / Lee, Rachel M / Hobson, Chad M / Chew, Teng-Leong / Stramer, Brian M

Developmental cell

2023 Volume 58, Issue 10, Page(s) 825–835.e6

Abstract: Forces controlling tissue morphogenesis are attributed to cellular-driven activities, and any role for extracellular matrix (ECM) is assumed to be passive. However, all polymer networks, including ECM, can develop autonomous stresses during their ... ...

Abstract	Forces controlling tissue morphogenesis are attributed to cellular-driven activities, and any role for extracellular matrix (ECM) is assumed to be passive. However, all polymer networks, including ECM, can develop autonomous stresses during their assembly. Here, we examine the morphogenetic function of an ECM before reaching homeostatic equilibrium by analyzing de novo ECM assembly during Drosophila ventral nerve cord (VNC) condensation. Asymmetric VNC shortening and a rapid decrease in surface area correlate with the exponential assembly of collagen IV (Col4) surrounding the tissue. Concomitantly, a transient developmentally induced Col4 gradient leads to coherent long-range flow of ECM, which equilibrates the Col4 network. Finite element analysis and perturbation of Col4 network formation through the generation of dominant Col4 mutations that affect assembly reveal that VNC morphodynamics is partially driven by a sudden increase in ECM-driven surface tension. These data suggest that ECM assembly stress and associated network instabilities can actively participate in tissue morphogenesis.
MeSH term(s)	Animals ; Drosophila/genetics ; Extracellular Matrix/physiology ; Morphogenesis/physiology ; Central Nervous System
Language	English
Publishing date	2023-04-21
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.2023.03.019
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Zs.A 5742: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Autocrine IL-6 drives cell and extracellular matrix anisotropy in scar fibroblasts.

Kenny, Fiona N / Marcotti, Stefania / De Freitas, Deandra Belo / Drudi, Elena M / Leech, Vivienne / Bell, Rachel E / Easton, Jennifer / Díaz-de-la-Loza, María-Del-Carmen / Fleck, Roland / Allison, Leanne / Philippeos, Christina / Manhart, Angelika / Shaw, Tanya J / Stramer, Brian M

Matrix biology : journal of the International Society for Matrix Biology

2023 Volume 123, Page(s) 1–16

Abstract: Fibrosis is associated with dramatic changes in extracellular matrix (ECM) architecture of unknown etiology. Here we exploit keloid scars as a paradigm to understand fibrotic ECM organization. We reveal that keloid patient fibroblasts uniquely produce a ... ...

Abstract	Fibrosis is associated with dramatic changes in extracellular matrix (ECM) architecture of unknown etiology. Here we exploit keloid scars as a paradigm to understand fibrotic ECM organization. We reveal that keloid patient fibroblasts uniquely produce a globally aligned ECM network in 2-D culture as observed in scar tissue. ECM anisotropy develops after rapid initiation of a fibroblast supracellular actin network, suggesting that cell alignment initiates ECM patterning. Keloid fibroblasts produce elevated levels of IL-6, and autocrine IL-6 production is both necessary and sufficient to induce cell and ECM alignment, as evidenced by ligand stimulation of normal dermal fibroblasts and treatment of keloid fibroblasts with the function blocking IL-6 receptor monoclonal antibody, tocilizumab. Downstream of IL-6, supracellular organization of keloid fibroblasts is controlled by activation of cell-cell adhesion. Adhesion formation inhibits contact-induced cellular overlap leading to nematic organization of cells and an alignment of focal adhesions. Keloid fibroblasts placed on isotropic ECM align the pre-existing matrix, suggesting that focal adhesion alignment leads to active anisotropic remodeling. These results show that IL-6-induced fibroblast cooperativity can control the development of a nematic ECM, highlighting both IL-6 signaling and cell-cell adhesions as potential therapeutic targets to inhibit this common feature of fibrosis.
MeSH term(s)	Humans ; Keloid/drug therapy ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Anisotropy ; Cells, Cultured ; Extracellular Matrix/metabolism ; Fibroblasts/metabolism
Chemical Substances	Interleukin-6
Language	English
Publishing date	2023-09-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1183793-7
ISSN	1569-1802 ; 0945-053X
ISSN (online)	1569-1802
ISSN	0945-053X
DOI	10.1016/j.matbio.2023.08.004
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Article ; Online: HIV risk behavior profiles among men who have sex with men interested in donating blood: Findings from the Assessing Donor Variability and New Concepts in Eligibility study.

Custer, Brian / Whitaker, Barbee I / Pollack, Lance M / Buccheri, Renata / Bruhn, Roberta L / Crowder, Lauren A / Stramer, Susan L / Reik, Rita A / Pandey, Suchitra / Stone, Mars / Di Germanio, Clara / Buchacz, Kate / Eder, Anne F / Lu, Yun / Forshee, Richard A / Anderson, Steven A / Marks, Peter W

Transfusion

2023 Volume 63, Issue 10, Page(s) 1872–1884

Abstract: Background: Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the ... ...

Abstract	Background: Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors. Study design and methods: Cross-sectional survey and biomarker assessment were conducted in eight U.S. cities. Participants were sexually active MSM interested in blood donation aged 18-39 years, assigned male sex at birth. Participants completed surveys during two study visits to define eligibility, and self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, one of the drugs in oral HIV pre-exposure prophylaxis (PrEP). Associations were assessed between HIV infection status or HIV PrEP use and behaviors, including sex partners, new partners, and anal sex. Results: A total of 1566 MSM completed the visit 1 questionnaire and blood draw and 1197 completed the visit 2 questionnaire. Among 1562 persons without HIV, 789 (50.4%) were not taking PrEP. Of those not taking PrEP, 66.2% reported one sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months. Conclusion: The study found that questions were able to identify sexually active, HIV-negative MSM who report lower risk sexual behaviors. About a quarter of enrolled study participants would be potentially eligible blood donors using individual risk assessment questions.
Language	English
Publishing date	2023-08-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.17515
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Article ; Online: Heterotypic contact inhibition of locomotion can drive cell sorting between epithelial and mesenchymal cell populations.

Brayford, Simon / Kenny, Fiona N / Hiratsuka, Toru / Serna-Morales, Eduardo / Yolland, Lawrence / Luchici, Andrei / Stramer, Brian M

Journal of cell science

2019 Volume 132, Issue 11

Abstract: Interactions between different cell types can induce distinct contact inhibition of locomotion (CIL) responses that are hypothesised to control population-wide behaviours during embryogenesis. However, our understanding of the signals that lead to cell- ... ...

Abstract	Interactions between different cell types can induce distinct contact inhibition of locomotion (CIL) responses that are hypothesised to control population-wide behaviours during embryogenesis. However, our understanding of the signals that lead to cell-type specific repulsion and the precise capacity of heterotypic CIL responses to drive emergent behaviours is lacking. Using a new model of heterotypic CIL, we show that fibrosarcoma cells, but not fibroblasts, are actively repelled by epithelial cells in culture. We show that knocking down EphB2 or ERK in fibrosarcoma cells specifically leads to disruption of the repulsion phase of CIL in response to interactions with epithelial cells. We also examine the population-wide effects when these various cell combinations are allowed to interact in culture. Unlike fibroblasts, fibrosarcoma cells completely segregate from epithelial cells and inhibiting their distinct CIL response by knocking down EphB2 or ERK family proteins also disrupts this emergent sorting behaviour. These data suggest that heterotypic CIL responses, in conjunction with processes such as differential adhesion, may aid the sorting of cell populations.
MeSH term(s)	3T3 Cells ; Animals ; Cell Communication/physiology ; Cell Line ; Cell Movement/physiology ; Cell Separation ; Contact Inhibition/physiology ; Embryonic Development/physiology ; Epithelial Cells/physiology ; Extracellular Signal-Regulated MAP Kinases/genetics ; Fibroblasts/physiology ; Fibrosarcoma/metabolism ; Humans ; Mesenchymal Stem Cells/physiology ; Mice ; Receptor, EphB2/genetics
Chemical Substances	EPHB2 protein, human (EC 2.7.10.1) ; Receptor, EphB2 (EC 2.7.10.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
Language	English
Publishing date	2019-05-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.223974
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Article ; Online: Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration.

Law, Ah-Lai / Jalal, Shamsinar / Pallett, Tommy / Mosis, Fuad / Guni, Ahmad / Brayford, Simon / Yolland, Lawrence / Marcotti, Stefania / Levitt, James A / Poland, Simon P / Rowe-Sampson, Maia / Jandke, Anett / Köchl, Robert / Pula, Giordano / Ameer-Beg, Simon M / Stramer, Brian Marc / Krause, Matthias

Nature communications

2021 Volume 12, Issue 1, Page(s) 5687

Abstract: Cell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate ... ...

Abstract	Cell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate it. However, so far, no direct negative regulators are known. Here we identify Nance-Horan Syndrome-like 1 protein (NHSL1) as a direct binding partner of the Scar/WAVE complex, which co-localise at protruding lamellipodia. This interaction is mediated by the Abi SH3 domain and two binding sites in NHSL1. Furthermore, active Rac binds to NHSL1 at two regions that mediate leading edge targeting of NHSL1. Surprisingly, NHSL1 inhibits cell migration through its interaction with the Scar/WAVE complex. Mechanistically, NHSL1 may reduce cell migration efficiency by impeding Arp2/3 activity, as measured in cells using a Arp2/3 FRET-FLIM biosensor, resulting in reduced F-actin density of lamellipodia, and consequently impairing the stability of lamellipodia protrusions.
MeSH term(s)	Actin-Related Protein 2-3 Complex/metabolism ; Animals ; Cell Line, Tumor ; Cell Movement ; Gene Knockout Techniques ; HEK293 Cells ; Humans ; Mice ; Proteins/genetics ; Proteins/metabolism ; Pseudopodia/physiology ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Wiskott-Aldrich Syndrome Protein Family/metabolism
Chemical Substances	Actin-Related Protein 2-3 Complex ; NHSL1 protein, human ; Proteins ; Recombinant Proteins ; WASF1 protein, human ; Wiskott-Aldrich Syndrome Protein Family
Language	English
Publishing date	2021-09-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-25916-6
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