To Divide or not to Divide? That is the Question Being Answered by Dlx Proteins in Developing Embryo Cells

By Victoria Sanderson

16 July 2019

Showing various stages of development of a chicken embryo

What do a healthy embryo and a cancerous tumor have in common? They both grow very quickly and use similar cell signalling pathways to know when to divide.

Tissue growth occurs as cells divide, increasing the total number of cells and the size of the tissue, whether that be an embryo or a tumor. During the early stages of embryonic development, cells divide very quickly to facilitate rapid growth. These dividing cells remain unspecialized until later in development. Cancer cells act in a similar fashion, proliferating at a very rapid rate. Not surprisingly, both embryonic and cancer cells use many of the same molecular signals to divide so quickly.

Prof. Andrew Bendall and his team in the Department of Molecular and Cellular Biology study a family of proteins that are key players in both embryonic development and cancer progression: the Dlx proteins. Unlike many of the other signals that occur in both cancer and embryogenesis, Dlx proteins act in two completely opposite ways in the developing embryo versus in cancer cells – but researchers don’t yet know why.

Previous studies have shown that Dlx proteins are highly expressed in cancer cells when compared to healthy cells. These proteins have a growth-promoting effect in cancer cells, essentially stepping on the gas pedal of cell division. On the other hand, research on developing embryos has shown that when Dlx proteins are present cell division is slowed, as if they are applying the brakes to cell division. This slowed division rate facilitates cell differentiation from non-specific stem cells into a more specialized cell type.

Bendall and MSc student Rachel MacKenzie recently published a study that begins to uncover how two members of the Dlx protein family (known as Dlx 5 and 6) slow cell division during chick embryogenesis, a novel insight that aids our understanding of Dlx protein function during healthy cell development.

Bendall and MacKenzie used several lines of evidence to explain how Dlx 5 and 6 slow cell division in several different types of non-cancerous cells. First, they determined that slowed cell growth was not a result of cell death or because the cells were entering quiescence, a hibernation-like cell state.  They then demonstrated that Dlx 5 and 6 cause a cell to remain “stalled” in a stage of the cell division cycle called G1. More specifically, the two proteins block progression past the G1-S checkpoint, which is a key turning point in cell division where the cell either commits to dividing or remains in the G1 stage to allow for differentiation, and this depends on the molecular signals present. While many of the signals involved in the progression through the G1-S checkpoint are well characterized, the addition of Dlx 5 and 6 as key players in certain cell types is a novel discovery.

Understanding how animals and humans develop is important in and of itself but developmental research, such as the work done in this study, can also improve our understanding of human birth defects, which are often the result of changes to the tightly controlled network of signals that control cell division and differentiation. It is also possible to link the genes and proteins that cells express in both development and cancer to understand how and why these signals pop up later in life, leading to new insights in cancer pathogenesis and potential diagnostic and therapeutic options.

While it is still not clear why Dlx proteins act so differently in embryonic and cancer cells, Bendall and his team hope to continue to help unlock this mystery by studying exactly how the Dlx proteins can block progression through the G1-S checkpoint leading to slowed cell division.

“I’m of the opinion that we will know more about what goes wrong in a cancer cell if we can understand what’s happening in a ‘normal’ cell,” explains Bendall.


Parvathy Ravi Sankar also contributed to this study.  Funding for this work was provided by the Natural Science and Engineering Research Council of Canada.


Read the full study in BMC Molecular and Cell Biology.

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