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  1. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Comparative Study of Contact Repulsion in Control and Mutant Macrophages Using a Novel Interaction Detection.

    Solís-Lemus, José Alonso / Sánchez-Sánchez, Besaiz J / Marcotti, Stefania / Burki, Mubarik / Stramer, Brian / Reyes-Aldasoro, Constantino Carlos

    Journal of imaging

    2020  Volume 6, Issue 5

    Abstract: In this paper, a novel method for interaction detection is presented to compare the contact dynamics of macrophages in ... ...

    Abstract In this paper, a novel method for interaction detection is presented to compare the contact dynamics of macrophages in the
    Language English
    Publishing date 2020-05-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2824270-1
    ISSN 2313-433X ; 2313-433X
    ISSN (online) 2313-433X
    ISSN 2313-433X
    DOI 10.3390/jimaging6050036
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Drosophila Embryonic Hemocytes Produce Laminins to Strengthen Migratory Response.

    Sánchez-Sánchez, Besaiz J / Urbano, José M / Comber, Kate / Dragu, Anca / Wood, Will / Stramer, Brian / Martín-Bermudo, María D

    Cell reports

    2017  Volume 21, Issue 6, Page(s) 1461–1470

    Abstract: The most prominent developmental function attributed to the extracellular matrix (ECM) is cell migration. While cells in culture can produce ECM to migrate, the role of ECM in regulating developmental cell migration is classically viewed as an exogenous ... ...

    Abstract The most prominent developmental function attributed to the extracellular matrix (ECM) is cell migration. While cells in culture can produce ECM to migrate, the role of ECM in regulating developmental cell migration is classically viewed as an exogenous matrix presented to the moving cells. In contrast to this view, we show here that Drosophila embryonic hemocytes deposit their own laminins in streak-like structures to migrate efficiently throughout the embryo. With the help of transplantation experiments, live microscopy, and image quantification, we demonstrate that autocrine-produced laminin regulates hemocyte migration by controlling lamellipodia dynamics, stability, and persistence. Proper laminin deposition is regulated by the RabGTPase Rab8, which is highly expressed and required in hemocytes for lamellipodia dynamics and migration. Our results thus support a model in which, during embryogenesis, the Rab8-regulated autocrine deposition of laminin reinforces directional and effective migration by stabilizing cellular protrusions and strengthening otherwise transient adhesion states.
    MeSH term(s) Animals ; Cell Movement ; Cells, Cultured ; Drosophila/growth & development ; Drosophila/metabolism ; Drosophila Proteins/metabolism ; Embryo, Nonmammalian/cytology ; Embryonic Development ; Extracellular Matrix/metabolism ; GTP Phosphohydrolases/metabolism ; Hemocytes/cytology ; Hemocytes/metabolism ; Laminin/metabolism ; Microscopy, Fluorescence ; Pseudopodia/physiology
    Chemical Substances Drosophila Proteins ; Laminin ; GTP Phosphohydrolases (EC 3.6.1.-) ; Rab8 protein, Drosophila (EC 3.6.1.-)
    Language English
    Publishing date 2017-11-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2017.10.047
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly.

    Dai, Jianli / Estrada, Beatriz / Jacobs, Sofie / Sánchez-Sánchez, Besaiz J / Tang, Jia / Ma, Mengqi / Magadán-Corpas, Patricia / Pastor-Pareja, José C / Martín-Bermudo, María D

    PLoS genetics

    2018  Volume 14, Issue 9, Page(s) e1007483

    Abstract: Basement membranes (BMs) are thin sheet-like specialized extracellular matrices found at the basal surface of epithelia and endothelial tissues. They have been conserved across evolution and are required for proper tissue growth, organization, ... ...

    Abstract Basement membranes (BMs) are thin sheet-like specialized extracellular matrices found at the basal surface of epithelia and endothelial tissues. They have been conserved across evolution and are required for proper tissue growth, organization, differentiation and maintenance. The major constituents of BMs are two independent networks of Laminin and Type IV Collagen in addition to the proteoglycan Perlecan and the glycoprotein Nidogen/entactin (Ndg). The ability of Ndg to bind in vitro Collagen IV and Laminin, both with key functions during embryogenesis, anticipated an essential role for Ndg in morphogenesis linking the Laminin and Collagen IV networks. This was supported by results from cultured embryonic tissue experiments. However, the fact that elimination of Ndg in C. elegans and mice did not affect survival strongly questioned this proposed linking role. Here, we have isolated mutations in the only Ndg gene present in Drosophila. We find that while, similar to C.elegans and mice, Ndg is not essential for overall organogenesis or viability, it is required for appropriate fertility. We also find, alike in mice, tissue-specific requirements of Ndg for proper assembly and maintenance of certain BMs, namely those of the adipose tissue and flight muscles. In addition, we have performed a thorough functional analysis of the different Ndg domains in vivo. Our results support an essential requirement of the G3 domain for Ndg function and unravel a new key role for the Rod domain in regulating Ndg incorporation into BMs. Furthermore, uncoupling of the Laminin and Collagen IV networks is clearly observed in the larval adipose tissue in the absence of Ndg, indeed supporting a linking role. In light of our findings, we propose that BM assembly and/or maintenance is tissue-specific, which could explain the diverse requirements of a ubiquitous conserved BM component like Nidogen.
    MeSH term(s) Adipose Tissue/cytology ; Adipose Tissue/metabolism ; Animals ; Animals, Genetically Modified ; Basement Membrane/physiology ; Drosophila/physiology ; Drosophila Proteins/physiology ; Female ; Fertility/physiology ; Male ; Membrane Glycoproteins/physiology ; Muscles/cytology ; Muscles/metabolism ; Mutation ; Organ Specificity/physiology ; Organogenesis/physiology ; Protein Domains/physiology
    Chemical Substances Drosophila Proteins ; Membrane Glycoproteins ; nidogen
    Language English
    Publishing date 2018-09-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1007483
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Tools Allowing Independent Visualization and Genetic Manipulation of

    Gyoergy, Attila / Roblek, Marko / Ratheesh, Aparna / Valoskova, Katarina / Belyaeva, Vera / Wachner, Stephanie / Matsubayashi, Yutaka / Sánchez-Sánchez, Besaiz J / Stramer, Brian / Siekhaus, Daria E

    G3 (Bethesda, Md.)

    2018  Volume 8, Issue 3, Page(s) 845–857

    Abstract: Drosophila ... ...

    Abstract Drosophila melanogaster
    Language English
    Publishing date 2018-03-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1534/g3.117.300452
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A Moving Source of Matrix Components Is Essential for De Novo Basement Membrane Formation.

    Matsubayashi, Yutaka / Louani, Adam / Dragu, Anca / Sánchez-Sánchez, Besaiz J / Serna-Morales, Eduardo / Yolland, Lawrence / Gyoergy, Attila / Vizcay, Gema / Fleck, Roland A / Heddleston, John M / Chew, Teng-Leong / Siekhaus, Daria E / Stramer, Brian M

    Current biology : CB

    2017  Volume 27, Issue 22, Page(s) 3526–3534.e4

    Abstract: The basement membrane (BM) is a thin layer of extracellular matrix (ECM) beneath nearly all epithelial cell types that is critical for cellular and tissue function. It is composed of numerous components conserved among all bilaterians [1]; however, it is ...

    Abstract The basement membrane (BM) is a thin layer of extracellular matrix (ECM) beneath nearly all epithelial cell types that is critical for cellular and tissue function. It is composed of numerous components conserved among all bilaterians [1]; however, it is unknown how all of these components are generated and subsequently constructed to form a fully mature BM in the living animal. Although BM formation is thought to simply involve a process of self-assembly [2], this concept suffers from a number of logistical issues when considering its construction in vivo. First, incorporation of BM components appears to be hierarchical [3-5], yet it is unclear whether their production during embryogenesis must also be regulated in a temporal fashion. Second, many BM proteins are produced not only by the cells residing on the BM but also by surrounding cell types [6-9], and it is unclear how large, possibly insoluble protein complexes [10] are delivered into the matrix. Here we exploit our ability to live image and genetically dissect de novo BM formation during Drosophila development. This reveals that there is a temporal hierarchy of BM protein production that is essential for proper component incorporation. Furthermore, we show that BM components require secretion by migrating macrophages (hemocytes) during their developmental dispersal, which is critical for embryogenesis. Indeed, hemocyte migration is essential to deliver a subset of ECM components evenly throughout the embryo. This reveals that de novo BM construction requires a combination of both production and distribution logistics allowing for the timely delivery of core components.
    MeSH term(s) Animals ; Basement Membrane/metabolism ; Basement Membrane/physiology ; Cell Movement/physiology ; Collagen/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster/embryology ; Drosophila melanogaster/metabolism ; Epithelial Cells/metabolism ; Extracellular Matrix/metabolism ; Extracellular Matrix/physiology ; Macrophages/metabolism
    Chemical Substances Drosophila Proteins ; Collagen (9007-34-5)
    Language English
    Publishing date 2017-11-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2017.10.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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