30 May 2022

Cells with multiple nuclei beneficial for evolutionary fitness of roundworms

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Cells with multiple nuclei are important for the evolutionary fitness of the roundworm, C. elegans. That is what the group of Matilde Galli concludes in a new paper, published in PLoS Biology on 24 May 2022. Having multiple nuclei enables intestinal cells to produce more of the proteins that function as nutrients for the worm’s offspring. “We believe these findings have broad significance for understanding tissue development,” says Galli.

Cells generally carry two copies of DNA in their nucleus. However, some cells contain more than two copies of genetic material. These are called polyploid cells. Polyploid cells play an important role in controlling organ size and metabolism, among other things. Interestingly, different types of polyploidies exist. Some polyploid cells contain one (often giant) nucleus in which they carry all copies of DNA – so-called single-nucleate cells. In other cells, the DNA copies are divided over multiple nuclei and these cells are therefore called multi-nucleate cells. Yet, the functional difference between single- and multinucleate cells was unknown until now.

Multiple nuclei

Researchers from the group of Matilde Galli used the roundworm C. elegans to compare animals that have mononucleated or binucleated (i.e., with two nuclei) intestinal cells, but the same total amount of DNA per cell. They found that worms with only mononucleated intestinal cells are evolutionary less fit: they give rise to fewer offspring in the long run. “It turns out that certain genes cannot be expressed Gene expression refers to the activity of a gene. The combination of active genes in a cell determines, amongst other things, the function, shape and size of the cell. at their full potential in cells that have one large nucleus instead of multiple nuclei, even if the number of DNA copies that the cells have is the same,” Galli explains.

Important nutrients

The worms without multinucleate cells are less efficient at reading out so-called vitellogenin genes. These genes contain the recipe for the production of yolk proteins, which are important nutrients for the progeny. The offspring of animals from single-nucleated parents inherits less yolk and was less fit. “It is quite striking that such a small difference – a cell having one instead of multiple nuclei, but the same amount of DNA – could have a detrimental effect on fitness,” says Galli.

Tissue development

The study, now published in PLoS Biology, is the first to directly compare single- and multinucleate polyploid cells. It contributes to the understanding of the function of polyploid cells, which are common and have important functions in for example tissue regeneration and damage responses. They are widespread in the mammalian heart, liver and placenta. “Given the widespread occurrence of multinucleated cells in both healthy and diseased tissues, we believe our findings have broad significance for understanding tissue development,” Galli concludes.


Endomitosis controls tissue-specific gene expression during development. Lotte M van Rijnberk, Ramon Barrull-Mascaró, Reinier L van der Palen, Erik S Schild, Hendrik C Korswagen, Matilde Galli. PLoS Biology, 2022.



Matilde Galli is Hubrecht Fellow at the Hubrecht Institute.