Biological implications of cell fusion

Ogle, Brenda M.; Cascalho, Marília; Platt, Jeffrey L.

doi:10.1038/nrm1678

Cited by 282 publications

(240 citation statements)

References 78 publications

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“…Th e fusion of trophoblast cells into a multinucleated ST constitutes a critical step in the process of placental development 1,41,43 . We therefore examined fusion and morphological changes in trophoblast cells in Bcl9l − / − placentas by electron microscopy.…”

Section: O C K S I C O N T R O L S I -C a T -1 M O C K S I C O N Tmentioning

confidence: 99%

“…C ell fusion is an essential and highly regulated event that occurs during development and tissue homeostasis, and is involved in such processes as fertilization, the formation of muscle fi bres and bone, development of the placenta in certain species (for example, Primata and Rodentia) and in the development of giant cells in chronic infl ammatory reactions 1,2 . Furthermore, recent studies have shown that cell fusion has a much broader role in tissue homeostasis and regeneration, such as in the fusion and transdiff erentiation of bone marrow-derived cells to neurons, hepatocytes, myocytes and epithelial cells in the intestine 1,3 .…”

mentioning

confidence: 99%

“…Furthermore, recent studies have shown that cell fusion has a much broader role in tissue homeostasis and regeneration, such as in the fusion and transdiff erentiation of bone marrow-derived cells to neurons, hepatocytes, myocytes and epithelial cells in the intestine 1,3 . Advances in the study of cell fusion in tissue repair and regeneration, particularly in infl ammatory conditions, have prompted the revival of an earlier theory, which postulates that cell fusion is one of the driving forces of cancer initiation and progression.…”

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confidence: 99%

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Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway

et al. 2011

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Cell fusion has a critical role in various developmental processes, immune response, tissue homeostasis and regeneration, and possibly, in cancer. However, the signals that regulate cell fusion remain poorly understood. In a screen for novel targets of Wnt / β -catenin signalling, we identifi ed glial cells missing 1 ( GCM1 ), which encodes a transcription factor that is involved in epigenetic regulation and is critical for the fusion of syncytiotrophoblast (ST) cells. Here we show that β -catenin / BCL9-Like (BCL9L) / T-cell factor 4 (TCF4) signalling directly targets the GCM1 / syncytin pathway and thereby regulates the fusion of human choriocarcinoma cells. Furthermore, we show that the GCM1 / syncytin-B pathway is signifi cantly downregulated in the placenta of BCL9L-defi cient mice and that the fusion and differentiation of ST-II cells are blocked. Our results demonstrate a signal transduction pathway that regulates cell fusion, and may provide intriguing perspectives into the various biological and pathological processes that involve cell fusion.

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Section: O C K S I C O N T R O L S I -C a T -1 M O C K S I C O N Tmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway

et al. 2011

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“…3,4 Because cell to cell fusion is a critical event in several biological processes such as fertilization, bone remodeling, muscle development, and stem cell differentiation, the topic has received significant interest. 5,6 Biomaterial-induced FBGC formation and the associated fibrous encapsulation result in a physical walling off effect that enhances material degradation and prevents appropriate molecular transport and vascularization. 1,7,8 We have recently described a requirement for the chemokine CCL2/MCP-1 in the formation of FBGCs.…”

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confidence: 99%

Foreign Body Giant Cell Formation Is Preceded by Lamellipodia Formation and Can Be Attenuated by Inhibition of Rac1 Activation

Jay

Skokos

Laiwalla

et al. 2007

The American Journal of Pathology

105

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Macrophages that are recruited to the site of implanted biomaterials undergo fusion to form surfacedamaging foreign body giant cells. Exposure of peripheral blood monocytes to interleukin-4 can recapitulate the fusion process in vitro. In this study, we used interleukin-4 to induce multinucleation of murine bone marrow-derived macrophages and observed changes in cell shape, including elongation and lamellipodia formation, before fusion. Because cytoskeletal rearrangements are regulated by small GTPases, we examined the effects of inhibitors of Rho kinase (Y-32885) and Rac activation (NSC23766) on fusion. Y-32885 did not prevent cytoskeletal changes or fusion but limited the extent of multinucleation. NSC23766, on the other hand, inhibited lamellipodia formation and fusion in a dose-dependent manner. In addition, we found that in control cells, these changes were preceded by Rac1 activation. However, NSC23766 did not block the uptake of polystyrene microspheres. Likewise, short interfering RNA knockdown of Rac1 limited fusion without limiting phagocytosis. Thus, phagocytosis and fusion can be partially decoupled based on their susceptibility to NSC23766. Furthermore, poly(ethylene-co-vinyl acetate) scaffolds containing NSC23766 attenuated foreign body giant cell formation in vivo. These observations suggest that targeting Rac1 activation could protect biomaterials without compromising the ability of macrophages to perform beneficial phagocytic functions at implantation sites. (Am J Pathol

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“…In contrast, cell fusion is normally restricted to a handful of processes, such as fertilization or formation of muscles, that involve predetermined cell types. 62 The accidental fusion of different somatic cells, as it happens during viral infections, 63 is akin to the marriage of randomly and blindly selected strangers, with similarly unexpected consequences. 44 …”

Section: Box 1: Terminologymentioning

confidence: 99%

The shock of being united and symphiliosis

Lazebnik

2014

Cell Cycle

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Biological implications of cell fusion

Cited by 282 publications

References 78 publications

Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway

Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway

Foreign Body Giant Cell Formation Is Preceded by Lamellipodia Formation and Can Be Attenuated by Inhibition of Rac1 Activation

The shock of being united and symphiliosis

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