Protein pathway competition regulates embryo development

One thing I’ve noticed in following scientific developments for a long time is that when something unexpected is discovered it very often adds to the complexity. Here’s a recent case in point, first, I’ll let a piece of the announcement speak for itself, and then I’ll explain the context:

Until now, scientists believed these pathways operated largely independently of one another to produce protein signals that travelled to the nuclei of the embryo’s cells where DNA is stored. There, coordination of these signals was thought to occur when they interacted with cell DNA to influence and control the expression of genes. Results published March 9 in the journal Current Biology, however, suggest that competition for the MAPK enzyme among proteins in different pathways influences which signals are sent to cells, establishing a biochemical mode of signal integration that adds a previously unrecognized layer of complexity and control to embryonic development [emphasis added].

[Source: Cell News]

The study, led by a team from Princeton University (New Jersey, USA), was researching the chains of chemical reactions – chemical pathways – that lead undifferentiated cells (stem cells) to the correct location, to develop the necessary characteristics, so that an embryo develops the appropriate organs and the correct form for its species. Most of this process, guided by what is called the regulated gene expression network, is studied by systems biology and at the molecular level is barely charted territory. (This also means there’s more chance for the unexpected.)

Specifically, the research team was studying the chemical pathways of protein formation, the building blocks of living tissue, and how they integrate different signals (chemical states) that direct early embryonic development. As the quote points out, it was believed that these pathways were separate, and communicated only with DNA in the nucleus of cells to receive instructions for development. The focus of attention was a particular enzyme (a chemical that enables or speeds-up reactions) known as MAPK (mitogen-activated protein kinase). The MAPK enzyme is found in all complex organisms, and appears in chemical networks that are critical for cell development.

The subject for their observations was the old lab-buddy the fruit fly (Drosophila melanogaster), whose embryos were used to study development. What they discovered was that different protein pathways competed for the MAPK enzyme. The competition didn’t necessarily have ‘winners’ and ‘losers’, but it was a competition for scarce resources, so that if one protein pathway was (for a time) more successful in acquiring MAPK, then whatever it was building would grow faster. This competition is a control mechanism. While the DNA may be making the blueprint, this control mechanism (or others like it) may determine the distribution of resources determining what grows where and when. The idea that proteins working together – even outside the instructions of DNA – may be guiding embryonic development is…unexpected. For embryology it could be revolutionary, although that overworked word should take on meaning only after a lot more testing and analyzing the findings.

The research team was able to track the effect of this competition for the MAPK enzyme. For example, the portion of the embryo that would become the fly’s head was where the concentration of protein from one pathway was high. That’s where MAPK would also be present in higher concentration than in another pathway protein, say at the tail of the fly.

Further work: Just two words, but in this case it’s like opening a dictionary, which you thought had a thousand pages but now has many thousand pages. Having broached the concept that protein pathways can produce signals that compete for enzyme (and possibly other) resources, and that this competition is yet another complication to the network of gene expression during embryo development…to a molecular biologist this might suggest all kinds of questions (experiments). How do the proteins compete? What determines how long one protein is more successful than another? Are there other enzymes that have similar relationships with signaling pathways? Is this same effect at work in other species? Many, many questions – with the potential to edit (if not re-write) the book on developmental biology.

In some ways, this suddenly expanding field of research sounds familiar – it echoes the discovery that within cells epigenetics (gene expression directed by something other than DNA, especially proteins) is much more complex and influential than originally thought. These are heady discoveries that quicken the pulse of veteran biologists and make PhD candidates salivate over dissertation topics. Much further work indeed.

Research Spectrum

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