Week 3 already?! It's hard to believe my last semester is passing me by so quickly!
One of the in-class assignments for my developmental biology class this past week was to read an article on positional information and how that information is perceived by the cells in the developing embryo to result in polarity, directional migration, and differentiation. The article spoke about the "French Flag" model for morphogen (extracellular agents that help to determine cell development) gradient formation, described in detail by Lewis Wolpert. This model is important representation of how a gradient can differentiate developing cells, but it certainly cannot be the entire story behind cellular positional information, as the article goes on to discuss (intercellular communication and regulation must also be at play).
A few specific examples of morphogens were provided, along with their typically understood function as they act in the developing embryo. Among them was the well-know (at least to developmental biologists) Dpp molecule. Decapentaplegic, or Dpp, is a morphogen that plays central roles in the development of the fruit fly embryo, specifically helping to differentiate the various imaginal discs (for example, wing disc) of the embryo, which later develop to form organs and limbs. Because this molecule is so important within embryology and has such widespread effects, I was curious about the details of its functionality. While the Wolpert et al. article talked a lot about mechanisms other then morphogens, I was more intrigued by the sensitive intricacies of a small concentration extracellular gradient possessing such omnipotence!
In my search for more information, I ran across a recent article by Zhou et al. seeking to understand more (among other things) about Dpp gradient formation. The authors point out that this is a difficult task, considering that gradients are usually present at extremely low concentration magnitudes, which can elicit confounding results from otherwise sound experimental procedure.
Without delving too deeply into the results of the paper, the authors suggest that Dpp gradient formation occurs firstly by simply diffusion, followed by a more complex process of cellular uptake and degradation, which helps to regulate the sensitive levels of Dpp in the extracellular matrix. It is this uptake process that pervious studies have failed to fully grasp, skewing previously accepted results about gradient formation.
A last comment provided by the authors urges us to recall that even if we understand how one morphogen functions, embryo development is a delicate symphony composed of entire suites of molecules, all in varying amounts and conformations. Each of these has a specific function, which can be altered by the presence and concentration of other morphogens. Understanding embryology from a single gradient is synonymous to extrapolating a comprehensive knowledge of the entire human brain from a single region. Cellular/molecular interplay and complex feedback pathway mapping is the name of the game here folks! So don't worry, there's a lot more science to be done!
Here are the articles to which I was referring throughout my entry:
Wolpert and Kerszberg (Positional Information).pdf
Zhou et al. (Extracellular Diffusion).pdf
Note: I am not claiming any rights to these articles by posting them. All copyright information can be found in the articles for the appropriate authors and publishers.