What I taught today: Position and Polarity

You really can't teach a class by lecturing at them…especially not an 8am class. But sometimes there is just such a dense amount of information that I have to get across before the students know what to ask that I have to just tell them some answers. My compromise to deal with this eternal problem is to mix it up; some days are lecture days, others are discussion days. And today was a discussion day.

I've been talking at them for the past two weeks, basically working to bring them up to a 1950s understanding of the field of developmental biology, with a glimmering of the molecular answers to come and some of the general concepts, so that they're equipped to start thinking about the contemporary literature. So I had them read this paper before class:

Kerszberg M, Wolpert L (2007) Specifying Positional Information in the Embryo: Looking Beyond Morphogens. Cell 130(2):205–209.

And then today they got into small groups and tried to explain it to each other. I primed them by suggesting that they try to define the terms positional information, gradient, morphogen, and polarity, and mentioned that I was playing a dirty trick on them, giving them a paper to introduce a basic concept that at the same time was pointing out some of the difficulties and problems of the idea, so I expected them to also do some critical thinking and question the concepts.

So they went at it. It went well; they had some lively conversations going on, which I always worry won't happen with early morning classes. I find it helpful to ask students to try to poke holes in an idea, rather than just recite by rote what the paper says — it sends them hunting rather than gathering.

Several students noted that having a simple continuum of a molecule begs the question of how that gets translated into many discrete cell types; why does having one concentration of a morphogen make a cell differentiate into a thorax, while a very slightly lower concentration means it differentiates into an abdomen? It's all well and good to suggest that a couple of overlapping gradients can specify position, like laying out a piece of graph paper with coordinates on it, but it doesn't explain how that gets translated into position-specific tissues. I was most pleased that several of them, while groping for an answer, related it to the lac operon in E. coli, and brought up the idea of thresholds of gene activation. Yay! That so sets up future discussions about early fly embryogenesis, where that is exactly the answer.

I think they also got the idea that an explanation for general specification of body parts, for example, may not apply for explaining polarity within a body part; we may have to think about some kind of hierarchy of regulation, where we progressively partition the embryo into smaller and smaller units, with different mechanisms at different scales. They might be catching on to the depths of the problems to come.

Another way the paper primed the students was that it very briefly introduces a whole bunch of specific molecules: dpp, bicoid, sonic hedgehog, activin. They got a very general idea of the broad roles these molecules play, all part of my devious grand plan. When we start talking about the details of how animals set up dorsal-ventral polarity, for instance, and dpp/BMP start coming up in more specific contexts, I want them to be familiar old friends — molecules they already knew casually and informally, and now see doing very specific things, and interacting with another set of molecules, which now also joins their circle of pals. Before I'm done with them, they're all going to regard these developmental signals and regulators as part of their family!