Is Intercellular Communication Via Gap Junctions Required for Myoblast Fusion?

Mège, René-Marc; Goudou, Danièle; Giaume, Christian; Nicolet, M.‐A.; Rieger, François

doi:10.3109/15419069409014208

Cited by 52 publications

(46 citation statements)

References 35 publications

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“…Few human cell types can fuse together and differentiate into multinucleated syncytia. This process is involved in the formation of myotubes (Constantin and Cronier, 2000;Mege et al, 1994;Wakelam, 1985), osteoclasts (Ilvesaro et al, 2000;Zambonin Zallone et al, 1984) and the syncytiotrophoblast (Midgley et al, 1963). Although they share a common morphological differentiation process, the three cell types that are able to differentiate into a syncytium differ notably.…”

Section: Discussionmentioning

confidence: 99%

“…Several lypophilic substances, such as aliphatic alcohols, and compounds isolated from liquorice roots (glycyrrhetinic acid) can uncouple gap junctional channels. Long-term incubation with heptanol considerably reduces the degree of fusion of cultured myoblasts (Constantin and Cronier, 2000;Mege et al, 1994) and preliminary studies showed that heptanol reversibly decreases gap junctional intertrophoblastic communication and trophoblastic cell fusion. Although its exact mechanism of action is not known, heptanol seems to decrease the fluidity of membranous cholesterol-rich domains (Johnston et al, 1980;Takens-Kwak et al, 1992) leading to a decrease of the open probability of junctional channels.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of connexin 43 in human trophoblast cell fusion and differentiation

Frendo

Cronier

Bertin

et al. 2003

Journal of Cell Science

127

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The syncytiotrophoblast is the principal component of the human placenta involved in feto-maternal exchanges and hormone secretion. The syncytiotrophoblast arises from the fusion of villous cytotrophoblasts. We recently showed that functional gap junctional intercellular communication(GJIC) is an important prerequisite for syncytiotrophoblast formation and that connexin 43 (Cx43) is present in cytotrophoblasts and in the syncytiotrophoblast. To determine whether Cx43 is directly involved in trophoblast fusion, we used an antisense strategy in primary cultures of human villous cytotrophoblasts that spontaneously differentiate into the syncytiotrophoblast by cell fusion. We assessed the morphological and functional differentiation of trophoblasts by desmoplakin immunostaining, by quantifying hCG (human chorionic gonadotropin) production and by measuring the expression of specific trophoblast genes (hCG and HERV-W). Furthermore, we used the gap-FRAP (fluorescence recovery after photobleaching) method to investigate functional GJIC. Cytotrophoblasts treated with Cx43 antisense aggregated and fused poorly. Furthermore, less HERV-W env mRNA, hCGβ mRNA and hCG secretion were detected in Cx43 antisense-treated cytotrophoblasts than in cells treated with scrambled antisense. Treatment with Cx43 antisense dramatically reduced the percentage of coupled trophoblast cells. Taken together, these results suggest that Cx43 is directly involved in human trophoblast cell-cell communication, fusion and differentiation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Involvement of connexin 43 in human trophoblast cell fusion and differentiation

Frendo

Cronier

Bertin

et al. 2003

Journal of Cell Science

127

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“…Alternatively, if diffusion of macromolecules is blocked in the α3 connexin knockout animals, it may suggest that connexin expression is required for the formation of the macromolecule permeable pathway. In this regard, it is interesting to note that gap junction mediated communication is a necessary prerequisite for successful myoblast fusion in the development of syncytial muscle cells (Mege et al, 1994) Interestingly, previous electron microscopic studies in lens fiber cells have suggested that gap-junction plaques may be the initiation site for lens membrane fusion (Kuszak et al, 1985). Future experiments in which α3 connexin (-/-) animals are crossed with TgN(GFPU)5Nagy mice should allow some of these questions to be resolved directly.…”

Section: Discussionmentioning

confidence: 99%

Development of a macromolecular diffusion pathway in the lens

Shestopalov

Bassnett

2003

Journal of Cell Science

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The mammalian lens consists of an aged core of quiescent cells enveloped by a layer of synthetically active cells. Abundant gap junctions within and between these cell populations ensure that the lens functions as an electrical syncytium and facilitates the exchange of small molecules between surface and core cells. In the present study, we utilized an in vivo mouse model to characterize the properties of an additional pathway, permeable to macromolecules, which co-exists with gap-junction-mediated communication in the lens core. The TgN(GFPU)5Nagy strain of mice carries a green fluorescent protein (GFP) transgene. In the lenses of hemizyous animals, GFP was expressed in a variegated fashion, allowing diffusion of GFP to be visualized directly. Early in development, GFP expression in scattered fiber cells resulted in a checkerboard fluorescence pattern in the lens. However, at E15 and later, the centrally located fiber cells became uniformly fluorescent. In the adult lens, a superficial layer of cells, approximately 100 μm thick, retained the original mosaic fluorescence pattern, but the remainder, and majority, of the tissue was uniformly fluorescent. We reasoned that at the border between the two distinct labeling patterns, a macromolecule-permeable intercellular pathway was established. To test this hypothesis, we microinjected 10 kDa fluorescent dextran into individual fiber cells and followed its diffusion by time-lapse microscopy. Injections at depths of >100 μm resulted in intercellular diffusion of dextran from injected cells. By contrast, when injections were made into superficial fiber cells, the injected cell invariably retained the dextran. Together, these data suggest that, in addition to being coupled by gap junctions, cells in the lens core are interconnected by a macromolecule-permeable pathway. At all ages examined, a significant proportion of the nucleated fiber cell population of the lens was located within this region of the lens.

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“…However, this study did not rule out the possibility that 18␤-glycyrrhetinic acid acted by other mechanisms, not involving gap junctions. On the other hand, many references evaluating dye or electrical coupling support the ability of 18␤-glycyrrhetinic acid and related agents to inhibit gap junctions, including dye coupling; a few are noted here (2,3,7,19,28,31,63).…”

mentioning

confidence: 99%

“…Octanol has been widely used and has been shown to block electrical and dye coupling in various cell types (1,5,9,16,28,31,33,35), but it failed to abolish slow waves in canine intestine CM (11). Like the glycyrrhetinic acid derivatives, octanol also affects ion channels, including Ca 2ϩ , Na ϩ , and Cl Ϫ channels (9,35).…”

mentioning

confidence: 99%

Do gap junctions play a role in nerve transmissions as well as pacing in mouse intestine?

Daniel

El-Yazbi²,

Mannarino³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Varicosities of nitrergic and other nerves end on deep muscular plexus interstitial cells of Cajal or on CD34-positive, c- kit-negative fibroblast-like cells. Both cell types connect to outer circular muscle by gap junctions, which may transmit nerve messages to muscle. We tested the hypotheses that gap junctions transmit pacing messages from interstitial cells of Cajal of the myenteric plexus. Effects of inhibitors of gap junction conductance were studied on paced contractions and nerve transmissions in small segments of circular muscle of mouse intestine. Using electrical field stimulation parameters (50 V/cm, 5 pps, and 0.5 ms) which evoke near maximal responses to nitrergic, cholinergic, and apamin-sensitive nerve stimulation, we isolated inhibitory responses to nitrergic nerves, inhibitory responses to apamin-sensitive nerves and excitatory responses to cholinergic nerves. 18β-Glycyrrhetinic acid (10, 30, and 100 μM), octanol (0.1, 0.3, and 1 mM) and gap peptides (300 μM of40Gap27,43Gap26,37,43Gap27) all failed to abolish neurotransmission. 18β-Glycyrrhetinic acid inhibited frequencies of paced contractions, likely owing to inhibition of l-type Ca2+channels in smooth muscle, but octanol or gap peptides did not. 18β-Glycyrrhetinic acid and octanol, but not gap peptides, reduced the amplitudes of spontaneous and nerve-induced contractions. These reductions paralleled reductions in contractions to exogenous carbachol. Additional experiments with gap peptides in both longitudinal and circular muscle segments after NG-nitro-l-arginine and TTX revealed no effects on pacing frequencies. We conclude that gap junction coupling may not be necessary for pacing or nerve transmission to the circular muscle of the mouse intestine.

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Is Intercellular Communication Via Gap Junctions Required for Myoblast Fusion?

Cited by 52 publications

References 35 publications

Involvement of connexin 43 in human trophoblast cell fusion and differentiation

Involvement of connexin 43 in human trophoblast cell fusion and differentiation

Development of a macromolecular diffusion pathway in the lens

Do gap junctions play a role in nerve transmissions as well as pacing in mouse intestine?

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