Trophoblast fusion: Fusogenic proteins, syncytins and ADAMs, and other prerequisites for syncytial fusion

Huppertz, Berthold; Bartz, C.; Kokozidou, Maria

doi:10.1016/j.micron.2005.12.011

Cited by 138 publications

(99 citation statements)

References 66 publications

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“…In one phase of the life cycle of villous trophoblast there is stable CTB-STB adhesion while, at a later stage, fusion occurs between a CTB and the overlying syncytium [55] (Figure 4a). …”

Section: Fusion During Trophoblast Differentiationmentioning

confidence: 99%

“…Gap junctional communication seems to be important in trophoblast fusion, which is impaired in primary CTB after Cx43 knockdown [46]. Other suggested membrane components implicated in fusion are syncytins, ADAMs (a disintegrin and metalloproteases), exposed annexin A5 and exposed (flipped) phosphatidylserine [55]. Syncytins are envelope (env) glycoproteins originating from viral sequences incorporated into the human genome.…”

Section: Fusion During Trophoblast Differentiationmentioning

confidence: 99%

“…ADAM12 mRNA is highly represented in placental cDNA libraries. The protein has been proposed as a mediator of fusion [55]. It has been shown to compensate for the dystrophin deficiency in mdx mice by redistribution of components of muscle cell-adhesion complexes [61].…”

Section: Fusion During Trophoblast Differentiationmentioning

confidence: 99%

See 2 more Smart Citations

Adhesion Molecules in Human Trophoblast – A Review. I. Villous Trophoblast

Aplin¹,

Jones²,

Harris³

2009

Placenta

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In the placental villus, cells attach to basement membrane via integrin α6β4 and adhere both laterally and apically to their neighbours. The most prominent adhesive specialisation seen in the electron microscope is the desmosome, which connects cytotrophoblast cells (CTB) laterally and also contributes to the attachment of CTB to the overlying syncytium.However, numerous cadherins and other junctional proteins are also present in the corresponding plasma membrane domains, indicating a multiplicity of adhesive interactions.Integrins, tight junction components and cadherins are all found in the syncytial microvillous membrane, perhaps reflecting its ability to form intersyncytial bridges. There is a wide gulf to be filled between molecular anatomy and functional studies, with much to be learned about the role of adhesion molecules in regulating villous epithelial integrity, homeostasis and growth.3

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“…In one phase of the life cycle of villous trophoblast there is stable CTB-STB adhesion while, at a later stage, fusion occurs between a CTB and the overlying syncytium [55] (Figure 4a). …”

Section: Fusion During Trophoblast Differentiationmentioning

confidence: 99%

Section: Fusion During Trophoblast Differentiationmentioning

confidence: 99%

See 1 more Smart Citation

Adhesion Molecules in Human Trophoblast – A Review. I. Villous Trophoblast

Aplin¹,

Jones²,

Harris³

2009

Placenta

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“…Several gene products that are expressed in villous trophoblast have been shown to be capable of mediating cell-cell fusion in cell lines. These include ADAM12 and the endogenous retroviral envelope proteins syncytin 1 and 2 (Huppertz et al, 2006a). Syncytin 2 is in villous cytotrophoblast (Kudaka et al, 2008;Malassine et al, 2007) while syncytin 1 is regulated by GCM-1 (Lin et al, 2005) and probably arises in intermediate cytotrophoblasts in advance of fusion, as well as being expressed in the syncytium (Huppertz et al, 2006a;Mi et al, 2000;Smallwood et al, 2003).…”

Section: Progression Of Villous Cytotrophoblast To Intermediate Statumentioning

confidence: 99%

Developmental cell biology of human villous trophoblast: current research problems

Aplin¹

2010

Int. J. Dev. Biol.

113

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The common gestational pathologies are placental and developmental in origin. However, much remains to be learned about the key events of morphogenesis and growth in the placenta. Metabolic settings established early in both the fetus and placenta define their capacity to respond to later challenges, as well as the quality of the response. Placental growth is exponential in the first trimester and involves coordinated events in trophoblast and mesenchyme, with early cell segregation events having a strong influence on growth potential. One of these is the differentiation of progenitor cytotrophoblasts into villous intermediate cells programmed to fuse with the syncytium, or, alternatively, into extravillous migratory cells that transform the maternal vascular supply. In the latter case, contact with decidual extracellular matrix stimulates differentiation, and therefore this decision is influenced by the number of contact sites at the placental periphery, which in turn is a function of branching in the villous tree. The villous trophoblast bilayer is the primary barrier between maternal and fetal tissues. The maternal-facing layer is syncytial and post-mitotic: this limits traffic of pathogens to the fetus and chimaerism arising by shedding of (non-proliferative) syncytial elements into maternal circulation. Conventional cell culture models fail to replicate this critical vectorial relationship. Tissue explants can overcome the problem to some extent, and have been used to show that turnover of trophoblast in the villous environment is regulated by signals from both fetal and maternal tissues. Maternally delivered insulin-like growth factors stimulate growth and might be therapeutically useful when endogenous growth pathways falter.

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“…Furthermore, within genes involved in the cellular movement function NiV induced the expression of ADAM 12 (FC=2,38). This protein is a metalloprotease proposed to function as a regulator of fusion of several cell types, including trophoblast and myoblast (Huppertz et al, 2006). This protein also modulates the cell fusion in giant cell tumors of long bones (Meng et al, 2005), by inducing actin cytoskeleton reorganization.…”

Section: Focus On Some Genes Of Interestmentioning

confidence: 99%