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Nematology,
2000]
In Caenorhabditis elegans almost all the epithelial cells fuse to form permanent syncytia. Cells in the vulva and hypodermis fuse autonomously to produce ring shaped cells with defined structures and functions. Analysis of temporal and spatial sequence of events together with ultrastructural characterisation of cell fusion intermediates show that fusion pores in specific domains of the membranes dilate and subsequently vesicles are formed. The fusomorphogenetic hypothesis states that these vesicles are targeted to different domains of the plasma membrane where they fuse, thereby causing changes in cell shape. It is proposed that cell fusion and polarised membrane recycling are involved in the formation of ring cells. Fusomorphogenesis is a working model to investigate the forces that drive pattern formation and generate diversity of developmental mechanisms in nematodes.
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Annu Rev Cell Dev Biol,
2014]
In biomembrane fusion pathways, membranes are destabilized through insertions of amphipathic protein segments, lipid reorganization via hemifusion, protein restructuring, and dimpling of the membranes. Four classes of membrane proteins are known in virus and cell fusion. Class I virus-cell fusion proteins (fusogens) are -helix-rich prefusion trimers that form coiled-coil structures that insert hydrophobic fusion peptides or loops (FPs or FLs) into membranes and refold into postfusion trimers. Class II virus-cell fusogens are -sheet-rich prefusion homo- or heterodimers that insert FLs into membranes, ending in postfusion trimers. Class III virus-cell fusogens are trimers with both -helices and -sheets that dissociate into monomers, insert FLs into membranes, and oligomerize into postfusion trimers. Class IV reoviral cell-cell fusogens are small proteins with FLs that oligomerize to fuse membranes. Class I cell-cell fusogens (Syncytins) were captured by mammals from retroviruses, and class II cell-cell fusogens (EFF-1/AFF-1) fuse membranes via homotypic zippering. Mechanisms and fusogens for most cell fusion events are unknown.
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Methods Mol Biol,
2008]
In the nematode Caenorhabditis elegans, 300 of the 959 somatic nuclei present in the adult hermaphrodite are located in syncytia. These syncytia are formed by the fusion of mononucleate cells throughout embryonic and postembryonic development. These cell fusions occur in a well-characterized stereotypical pattern, allowing investigators to study many cell fusion events at the molecular and cellular levels. Using tools that allow visualization of cell membranes, cell junctions, and cell cytoplasm during fusion, genetic screens have identified many C. elegans cell fusion genes, including those that regulate the fusion cell fate decision and two genes that encode components of the cell fusion machinery.
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Dev Dyn,
2000]
Cell fusion is a universal process that occurs during fertilization and in the formation of organs such as muscles, placenta, and bones. Very little is known about the molecular and cellular mechanisms of cell fusion during pattern formation. Here we review the dynamic anatomy of all cell fusions during embryonic and postembryonic development in an organism. Nearly all the cell fates and cell lineages are invariant in the nematode C. elegans and one third of the cells that are born fuse to form 44 syncytia in a reproducible and stereotyped way. To explain the function of cell fusion in organ formation we propose the fusomorphogenetic model as a simple cellular mechanism to efficiently redistribute membranes using a combination of cell fusion and polarized membrane recycling during morphogenesis. Thus, regulated intercellular and intracellular membrane fusion processes may drive elongation of the embryo as well as postembryonic organ formation in C. elegans. Finally, we use the fusomorphogenetic hypothesis to explain the role of cell fusion in the formation of organs like muscles, bones, and placenta in mammals and other species and to speculate on how the intracellular machinery that drive fusomorphogenesis may have evolved.
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Development,
2017]
Cell-cell fusion is essential for fertilization and organ development. Dedicated proteins known as fusogens are responsible for mediating membrane fusion. However, until recently, these proteins either remained unidentified or were poorly understood at the mechanistic level. Here, we review how fusogens surmount multiple energy barriers to mediate cell-cell fusion. We describe how early preparatory steps bring membranes to a distance of 10nm, while fusogens act in the final approach between membranes. The mechanical force exerted by cell fusogens and the accompanying lipidic rearrangements constitute the hallmarks of cell-cell fusion. Finally, we discuss the relationship between viral and eukaryotic fusogens, highlight a classification scheme regrouping a superfamily of fusogens called Fusexins, and propose new questions and avenues of enquiry.
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Bioessays,
2003]
The ability of two or more cells to unite to form a new syncytial cell has been utilized in metazoans throughout evolution to form many complex organs, such as muscles, bones and placentae. This requires migration, recognition and adhesion between cells together with fusion of their plasma membranes and rearrangement of their cytoplasmic contents. Until recently, understanding of the mechanisms of cell fusion was restricted to fusion between enveloped viruses and their target cells. The identification of new factors that take part in developmental cell fusion in C. elegans opens the way to understanding how cells fuse and what the functions of this process are. In this review, we describe current knowledge on the mechanisms and putative roles of developmental cell fusion in C. elegans and how cell fusion is regulated, together with other intercellular processes, to promote organogenesis.
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Adv Exp Med Biol,
2011]
In normal development cell fusion is essential for organ formation and sexual reproduction. The nematode Caenorhabditis elegans has become an excellent system to study the mechanisms and developmental functions of cell-to-cell fusion. In this review we focus on the heterochronic regulation of cell fusion. Heterochronic genes control the timing of specific developmental events in C. elegans. The first microRNAs discovered were found as mutations that affect heterochronic development and cell-cell fusions. In addition numerous heterochronic transcription factors also control specific cell fusion events in C. elegans. We describe what is known about the heterochronic regulation of cell fusion of the epidermal seam cells. The fusogen AFF-1 was previously shown to mediate the fusion of the lateral epidermal seam cells. Here we provide evidence supporting the model in which LIN-29, the heterochronic Zinc-finger transcription factor that controls the terminal fusion of the seam cells, stimulates AFF-1 expression in the seam cells before they fuse. Therefore, the heterochronic gene LIN-29 controls AFF-1-mediated cell-cell fusion as part of the terminal differentiation program of the epidermal seam cells.
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Dev Dyn,
2010]
Eukaryotic cells have evolved diverged mechanisms to merge cells. Here, we discuss three types of cell fusion: (1) Non-self-fusion, cells with different genetic contents fuse to start a new organism and fusion between enveloped viruses and host cells; (2) Self-fusion, genetically identical cells fuse to form a multinucleated cell; and (3) Auto-fusion, a single cell fuses with itself by bringing specialized cell membrane domains into contact and transforming itself into a ring-shaped cell. This is a new type of selfish fusion discovered in C. elegans. We divide cell fusion into three stages: (1) Specification of the cell-fusion fate; (2) Cell attraction, attachment, and recognition; (3) Execution of plasma membrane fusion, cytoplasmic mixing and cytoskeletal rearrangements. We analyze cell fusion in diverse biological systems in development and disease emphasizing the mechanistic contributions of C. elegans to the understanding of programmed cell fusion, a genetically encoded pathway to merge specific cells.
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Trends Cell Biol,
2007]
Most readers of this review originated from a sperm-egg fusion event. Cell fusion is a process that is crucial at many intersections later during development. However, we do not know which molecules (fusogens) fuse the membranes of gametes to form zygotes, myoblasts to form myotubes in muscles, macrophages to form osteoclasts in bones, or cytotrophoblasts to form syncytiotrophoblasts in placentas. There are five gold standards that can be applied for the identification of genuine fusogens. Based on these criteria, a numerical score can be used to assess the likelihood of protein fusogenicity. We compare distinct families of candidate developmental, viral and intracellular fusogens and analyze current models of membrane fusion.