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In biology, a syncytium is a large region of cytoplasm that contains many nuclei. "It is a large cell-like structure formed by the joining together of two or more cells. The plural is syncytia."¹

A syncytium can form in two ways. Many insects such as the model organism Drosophila melanogaster lay eggs that initially develop as syncytial blastoderms, i.e early on the embryos exhibit incomplete cell division. In particular, the nuclei undergo S-phase (they replicate their DNA) and sister chromatids get pulled apart and re-assembled into nuclei containing full sets of homologous chromosomes, but cytokinesis is absent. Thus, the nuclei multiply in a common cytoplasmic space of the zygote. Large skeletal muscle fibers form by the fusion of thousands of myocytes.

A syncytium occurs most simply when a cell divides without undergoing cytokinesis. This is most common in cancer cells because they are non-functional.

The early embryo syncytium of invertebrates such as Drosophila is important for syncytial specification of cell differentiation. The egg cell cytoplasm contains localized mRNA molecules such as those that encode the transcription factors Bicoid and Nanos. Bicoid protein is expressed in a gradient that extends from the anterior end of the early embryo while Nanos protein is concentrated at the posterior end (antero-posterior axis). At first, the nuclei of the early embryo rapidly and synchronously divide in the syncytial blastoderm and then migrate through the cytoplasm and position themselves in a monolayer around the periphery, leaving only a small number of nuclei in the center of the egg, which will become yolk nuclei. The position of the nuclei along the embryonic axes determines the relative exposure of different amounts of Bicoid, Nanos, and other morphogens. Those nuclei with more Bicoid will activate genes that promote differentiation of cells into head and thorax structures. Nuclei exposed to more Nanos will activate genes responsible for differentiation of posterior regions, such as the abdomen and germ cells. The same principles hold true for the specification of the dorso-ventral axis – higher concentration of nuclear Dorsal protein on the ventral side of the egg specify the ventral fate, whereas absence thereof allows dorsal fates. After the nuclei are positioned in a monolayer underneath the egg membrane, the membrane begins to slowly invaginate, thus separating the nuclei into cellular compartments; during this period, the egg is called a cellular blastoderm. The pole cells – the germline anlage – are the first cells to separate fully.

The syncytium of skeletal muscle is important because it allows rapid coordinated contraction of muscles along their entire length. Action potentials propagate along the surface of the muscle fiber from the point of synaptic contact with a motorneuron.

The multinucleated (syncytium) arrangement of skeletal muscle is important in pathologic states such as myopathy, where focal necrosis (death) of a portion of a skeletal muscle cell does not result in necrosis (death) of the adjacent sections of that same skeletal muscle cell (since those adjacent sections have their own nuclear material). Thus, myopathy is usually associated with such "segmental necrosis", but with some of the surviving segments being functionally cut off from their nerve supply via loss of continuity with the neuromuscular junction.

Another important vertebrate syncytium is in the placenta of placental mammals. Embryo-derived cells that form the interface with the maternal blood stream fuse together to form a multi-nucleated barrier. This is probably important in order to limit the exchange of migratory cells between the developing embryo and the body of the mother, as some blood cells are specialized to be able to insert themselves between adjacent epithelial cells. The syncytial epithelium of the placenta does not provide such an access path from the maternal circulation into the embryo.

Syncytium caused by HSV-1 infection in Vero cells

Syncytia can also form when cells are infected with certain types of virus such as H.I.V. and paramyxoviruses. During infection, viral fusion proteins used by the virus to enter the cell are transported to the cell surface where they can cause the host cell membrane to fuse with neighbouring cells.

In HIV infection, the virus can infect a T-helper lymphocyte. Then, the leukocyte begins to display surface HIV glycoproteins, which are antigenic. Normally, a T-cytotoxic lymphocyte will immediately come to "inject" lymphotoxins that will kill the infected T-helper, such as perforin or granzyme. However, if there are nearby T-helper cells, the GP-41 HIV receptors displayed on the surface of the T-helper will bind to other similar lymphocytes. This makes dozens of T-helpers fuse cell membranes into a giant, nonfunctional syncytium, which allows the HIV virus to kill many T-helpers by infecting only one.

• Syncytiotrophoblast
• Atrial syncytium

¹ National Cancer Institute