Richard Gordon, Transmogrifying from Virtual to Physical, Brought us Bits of Embryogenesis

I was honored to be able to bring Dr. Richard (Dick) Gordon to the Michigan State campus for a seminar on April 9 (see video on Vimeo). Currently at the Gulf Specimen Marine Laboratory (and retired from the University of Manitoba), Dick is a theoretical development biologist of the highest caliber [1]. He gave a talk entitled "Cause and Effect in the Interaction between Embryogenesis and the Genome" [2]. He even brought toys [3] to illustrate his theory of cellular differentiation.

Dick's virtual world avatar (Paleo Darwin) is seated in the middle picture.

Dick Gordon, master collaborator.

The theoretical model he presented suggests that differentiation waves [4] pulse through the embryo during development, which set up spatially-restricted gene expression and differentiation into distinct cellular types. According to this view, each cell's differentiation is a binary and recursive process (e.g. one "decision" point building upon another), and is contingent upon the cell's position and environment. In this sense, higher-level organization (e.g. modules) are not caused by gene expression. Rather, gene expression changes that lead to observable phenotypic modules [5] and other patterns are caused by the extracellular environment of a developing organism.

An example of a Wurfel toy, taken from a slide in his talk. A fine example of Canadian innovation.

There were many profound moments in this lecture. An overarching theme of the talk was how candidate ideas (e.g. hypotheses) are tested, implemented, and critically examined in the course of doing science. One of these was the "organizer" experiments of Hans Spemann [6], in which a piece of tissue transplanted to an embryo can induce the formation of a second animal. Subsequent experiments have shown that while transplanted tissue accomplishes this, other transplanted materials (even some which are non-organic) can induce this response as well. Perhaps the effect is not due to the tissue itself, but the hydrophobicity or hydrophilicity of the materials transplanted. This might be characterized as a special case of Type I error due to incomplete experimental information [7].

Picture of Hans Spemann (inducers).

Another candidate idea presented was Alan Turing's notion of "morphogens". Morphogens are hypothetical molecules proposed by Turing to drive pattern formation in a developing organism [8]. According to the talk, morphogens are not the causal factor for morphogenesis, nor are genetic regulatory cascades. Instead, they are both driven by expansion and contraction waves that course through the embryo. These waves (which have been observed) also trigger the mechanisms of differentiation (e.g. signaling molecules and gene expression changes) in cells. A good example of the problems related to establishing causality in a complex systems.

Picture of Alan Turing (morphogens).

Time-course (and illustration) of differentiation waves moving across an embryo from the talk.

After the talk, Dick and I discussed the possible role of differentiation wave-like activity in the process of in vitro (or perhaps even in vivo) cellular reprogramming (the controlled phenotypic transformation of a cell from one phenotype to another). Interesting stuff, and as always, you are welcome to participate in the Embryo Physics course [9], which is made possible by a fine group of people. Please contact myself or Dick if you are interested in presenting.

The scene of the crime, so to speak. Some quiet moments before my virtual lecture (Scenes from a Graphical, Parallel Biological World) given in April, 2012.

NOTES:

[1] He was originally trained in chemical physics at the University of Oregon (home of the Oregonator). See his Google Scholar profile for more information. According to their records, he has a h-index of 32 (which is quite impressive). He also has an Erdos number of 2i (long story).

Animation of the Oregonator (activator/inhibitor system). COURTESY: Scholarpedia.

[2] Here is a link to the version of this talk (.pdf slides) presented in the Embryo Physics course on March 20, 2012.

[3] One of these was a Wurfel, which is a bunch of wooden blocks joined together with an elastic string. I own one of these, and before this lecture I had no idea as to its name!

The Wurfel was used to demonstrate the configurational constraints and opportunities afforded to the genome due to a cell's biophysical and epigenetic context. For more fun (and combinatorics) with puzzles, please see the following blog post: Puzzle Cube. Paleotechnologist blog, August 31 (2011).

[4] According to his talk, these may either be calcium waves or something functionally similar. For an introduction to embryonic calcium waves (and how to image them), please see:

Gillot, I. and Whittaker, M.   Imaging Calcium Waves in Eggs and Embryos. Journal of Experimental Biology, 184, 213–219 (1993).

[5] Here is a video from Jeff Clune (University of Wyoming) demonstrating how modularity might have evolved using the software platform HyperNEAT (evolutionary neural networks). Based on the following paper:

Clune, J., Mouret, J-B., and Lipson, H.   The evolutionary origins of modularity. Proceedings of the Royal Society B, 280, 2012-2863 (2013).

[5] Here is a YouTube video that explains Spemann's organizer experiments in more detail.

[6] This fits very much within the scope of the Hard-to-define-Events (HTDE) approach. For more information, please see the HTDE 2012 workshop website.

[7] Here are some examples of morphogenesis (sensu Turing) the morphogen concept modeled using the Gro programming language (from the Klavins Lab, University of Washington).

The morphogen concept was some of Turing's later work. Even though Turing was a computing pioneer, his coupled reaction-diffusion model of chemical morphogenesis have become a prevailing view of how developmental morphogenesis proceeds. However, these ideas are also useful in the computational modeling of textures. See Turing's classic paper for more information:

Turing, A.M.   The Chemical Basis of Morphogenesis. Philosophical Transactions of the Royal Society of London, 237 (641), 37–72 (1952).

[8] While not formally a MOOC, the Embryo Physics course is an example of distributed learning. For more information, watch for the forthcoming paper:

Gordon, R.   The Second Life Embryo Physics Course. Systems Biology in Reproductive Medicine, x(x), xxx-xxx (2013).