Our skin has a complex structure consisting of many cell layers. The very periphery of skin is lined with cells that are continuously shed and replaced by new ones. These outer cells are “terminally differentiated”, meaning that they are no longer able to divide, and are instead replenished from an inner layer of “basal progenitor cells”, a type of stem cell. When a cell divides in the process of mitosis it forms two daughter cells, and for these basal progenitor cells the process is asymmetric—rather than producing two identical cells it produces one basal progenitor, essential for new growth, and one which becomes a terminally differentiated outer cell. The balance between growth and differentiation is very important for skin cells, as too much growth can lead to cancer, whilst too much differentiation can lead to ageing and poor wound healing.
A research group at Rockefeller University recently led an investigation into which specific genes are responsible for controlling this balance between growth and differentiation. They looked at the skin of developing mice and identified which genes were expressed differently in both the differentiation process and epithelial cancer. They identified 87 different genes, but later narrowed their focus to only one of those—a gene called Pex11b.
Inside cells there are many types of organelles, including mitochondria, lysosomes, and peroxisomes, which are essential to cell health. There are many copies of each organelle type in a cell and during mitosis it is important that they are divvied up between both daughter cells. Peroxisomes are important as they carry out a range of metabolic reactions and the Pex11b gene the group identified was found to code for a peroxisomal protein. When the expression of Pex11b was “knocked down”, the peroxisomes could still function, but the skin of the developing mice did not form properly, indicating the importance of Pex11b in differentiation.
The researchers then looked specifically at the process of mitosis. Normally, replicated chromosomes are pulled apart by structures called spindle fibers, and the peroxisomes cluster around the ends of these spindle fibers. However, when Pex11b was knocked down the peroxisomes did not cluster and did not segregate evenly between daughter cells. In addition, the alignment of the spindle fibres was abnormal and cell division took much longer. Finally, the researchers used a special technique to induce a change in peroxisome positioning in normal cells, which had the same effect as knocking down Pex11b.
From this the researchers concluded that the position of peroxisomes, and probably other organelles, is important in regulating mitosis. They think that this is particularly important in the asymmetric cell division in skin, causing abnormal skin development in mice when it is disrupted.
Asare, A., Levorse, J., & Fuchs, E. (2017). Coupling organelle inheritance with mitosis to balance growth and differentiation. Science, 355(6324), eaah4701.
(Featured image courtesy of Ed Uthman on Flickr)