Functional significance and remodeling challenges of polyploidy across the lifetime of epithelial tissues

Animal cells have characteristic structures that support their biological roles. For example, epithelial cells adhere tightly to their neighbors to form sheets of tissue, a structure that supports barrier functions such as with the skin as an outer protective layer, or the lining of the gut. One aspect of cell structure is the nucleus and its size.

While most cells are diploid, with a copy of the genome from each parent, certain cells become polyploid, with many copies of the genome within a single nucleus. This leads to large nuclei and proportionately large cells. What are the benefits and costs of polyploidy?

Polyploid cells occur in the liver, muscles, and maternal and extra-embryonic tissues, such as those that support placental development at the mother-fetus interface. Benefits include barrier tissue maintenance and repair after wounding. Wound repair involves polyploid cells becoming even larger to help cover the wound site.

Also, having many copies of the genome supports rapid, efficient production of needed proteins, such as from placental genes that promote maternal milk production. However, there is not always a clear correlation between DNA copy number and actual protein output, and under experimental conditions some tissues seem to also function without being polyploid.

Thus, investigation of additional tissue types is needed to better understand the hypothesized benefits of polyploidy.

On the other hand, polyploidy also poses challenges to cells. In some cases, the entire cell's genome is not copied, but only DNA regions containing certain genes. This is an efficient way to support rapid production when only the specific proteins from those genes are needed.

Yet, this partial increase in DNA copies is an unstable arrangement that usually triggers programmed cell death, known as apoptosis, as a form of biological quality control. Polyploid cells therefore require special genetic properties to suppress this. One key research system where this has been explored is the fruit fly Drosophila melanogaster, a powerful genetics model species.

However, we discovered that critical genes for controlling programmed cell death, the so-called Grim Reaper genes, are a unique feature in flies. It remains unknown which genes serve this function in other animals. Also, one hallmark of cancer cells is that they have unstable DNA arrangements yet somehow evade programmed cell death.

Research in new species on how polyploid cells handle the programmed cell death issue will identify critical genes and could help improve our understanding of genetics relevant to cancer treatment.

In this research project, we will test the hypothesized benefits (barrier tissue structure, rapid protein production) and examine the potential risks (unstable DNA arrangement, need to block cell death) of polyploidy in a novel biological system: the two extra-embryonic tissues of the flour beetle Tribolium castaneum. These tissues serve epithelial barrier functions by surrounding and protecting the embryo.

The serosa surrounds the embryo and yolk while the amnion, like its namesake in mammals, forms a fluid-filled, inner cavity. The serosa also has a rapid production role to make a cuticle layer that reinforces the eggshell. Notably, these tissues are stable and polyploid for most of their lifetime, and then they actively uncover the embryo and precisely undergo cell death.

We have developed methods to investigate polyploidy in the beetle, including genome sequencing and live imaging microscopy that reveals healthy and experimentally perturbed barrier tissue structure. The serosa and amnion offer an excellent comparative system. Our preliminary work suggests that the serosa is capable of increased polyploidy to compensate in genetic models of wound-like tissue impairment while the amnion is not.

This paves the way to better understanding of tissue-specific features of polyploidy and to uncover new critical genes involved in polyploidy control.