I’m going to get off a quick summary of this afternoon’s talks, then I have to run down to the poster session to find out what the grad students have been doing. Are we having fun yet? I’m going to collapse in bed tonight, and then unfortunately I have to catch an early flight back home, so I’m going to miss a lot of cool stuff tomorrow.
First up after lunch was Deneen Wellik, who summarized her work with Hox genes and patterning the vertebrate axial skeleton. I’m spared some effort here — I already wrote up her paper, so read that for the whole story. In short, one of the confounding things about studying the Hox genes is that there are four banks of them, so there is a lot of redundancy; knocking out just one has fairly subtle effects. Wellik has been deleting whole sets of Hox genes in mice, and finding that their loss creates homeotic transformations of regions of vertebrae into more anterior regions.
Daniel Meulemans described Gene regulatory novelty and the origins
of the vertebrate head skeleton. Much of the vertebrate skull is the product of neural crest cells and ectodermal placodes. Meulemans was looking for the origins of these cranial innovations by comparing gene expression in the cephalochordate Amphioxus and the lamprey, and found that certain classes of genes, specifically those involved in specifying neural crest tissue, were expressed in lampreys but not in Amphioxus at the time and place where neural crest would form. This was not just a descriptive, correlational study, though — he also carried out overexpression and rescue experiments. In the lamprey, one experiment is to over-express genes involved in neural crest specification, which causes more cells to be recruited into the neural crest population and produces an assayable surge in those cells. Injecting extra copies of the Amphioxus SoxE and Snail genes did the same thing, producing more neural crest. In addition, there is a zebrafish mutant that has lost the homologous Sox10 gene — these mutants have no pigmentation or enteric neurons, both of which are derived from neural crest. Injecting Amphioxus SoxE rescues the zebrafish mutant; it appears that the Amphioxus gene is fully equivalent to the zebrafish gene. So why does Amphioxus lack neural crest? One reason is because other regulators are not present in Amphioxus to activate SoxE and other neural crest associated genes.
Detlev Arendt told a familiar story about Evolution of the central nervous
system in animals. He works on a polychaete worm, Platynereis, and his story was that we have astonishing similarities between chordates and this worm in the molecular markers that distinguish certain specific cell types in our brains. I’ve also written up a couple of his papers, one on the homologies in the CNS of worms and chordates, and another on his work with evolution of the eye. This was good stuff, but I’d been conditioned at this time by some of the earlier talks to think that we definitely need more taxa in these comparisons — it’s a strong story that will be even stronger with some more intermediates.
Fred Nijhout sort of blew me away with Multiple and diverse mechanisms for
robustness in a complex network. It wasn’t at all what I expected: it was solid biochemistry. Whoa. I really had to strain my brain to keep up, but it was fascinating stuff that I’ll have to digest for some time. One of the big issues in developmental biology is robustness or canalization, a property of many systems which exhibit remarkable consistency and flexibility in the face of environmental and genetic challenges. You can knock out significant genes, or expose them to utterly horrible environmental conditions, and embryos tend to go ahead and produce fairly normal organisms (in most cases; they can also fail spectacularly). So the question is how do embryos do that?
Nijhout took a very different approach to this problem. What we need is a specific developmentally significant pathway which is well understood, complex but not too complex, and that can be approached mathematically. He’s looking at one carbon metabolism. Metabolism! It’s biochemistry! He was talking about enzyme kinetics! I was flashing back to my junior year in college, when I lived immersed in charts of biochemical pathways … it wasn’t an entirely pleasant feeling.
But it was OK, there was some familiar ground. The one carbon metabolism pathway is a set of reactions that are important in DNA synthesis and repair, DNA and histone methylation, dopamine and serotonin metabolism, and responses to oxidative stress — it’s a pathway with fingers in lots of pies, being involved in cancer, neurobehavioral disorders, cell division, and development. This is the pathway in which folate is central; it’s why pregnant women need to take a sufficient amount of folic acid, to prevent neural tube defects. So what Nijhout has done is to quantitatively model the whole pathway, using the known properties of the enzymes, substrate concentrations, etc., and showed that it exhibits developmental robustness. Plug in extra amino acids, just as typically happens after you eat a meal, and some parts of the system respond with wild variations in concentrations and reaction rates, but key parts are stabilized, with, for instance, purine and pyrimidine synthesis chugging along at a steady pace. And of course the real virtue is that he could trace the process through the pathway and show exactly and quantitatively how the biochemistry dictated that behavior. It was hard stuff for someone unaccustomed to talks in biochemistry, but a good way to stretch the mind.
OK, now the posters. This is going on until 10:00 local time, which is midnight to my midwestern clocks — I’m going to have to hope my stamina holds up here.
Fred is a genius! He always has something new to blow your mind. I hope that once you get back home and rest, you will write some more detailed posts about some of the talks.
You mean… networks that are reducibly complex?
OK, I still got nothing intelligent to say.
Science!
It would have been interesting to hit UO today (Saturday) and see if I could say hi to you, PZ – especially since it was such a suck-ass day and I was over by UO anyway. Hope you enjoy water, as a cephalopod should.
I don’t have anything intelligent to say either, but I will highly recommend reading the article write-ups that PZ linked. I found them fascinating and remarkably accessible, with several pretty pictures that also happened to be full of information.
I have two questions from the write-ups:
1) Sonic Hedgehog is really the full name of the Shh protein, not a clever mnemonic or some in-joke?
2) How could a “Mathematician” like Dembski and his “Biologist” friends like … Wells? read articles such as those that PZ summarized without being absolutely fascinated? (I assume they don’t get _less_ interesting when you are at least familiar with all of the terms.)
One more question, am I the only one twisted enough to want to see pictures of the Franken-mice from the Hox genes article? Assuming any lived to term, of course..
yes, shh = sonic hedgehog – it’s a major player in neural tube development.
the quirky names are part of the fun of being a developmental biologist – although you’d be amazed how quickly the names seem normal. I like to bug my nematode geneticist colleagues about their rather dull nomenclature (Unc-112, Unc-113, etc – boring).
I’ll admit to being partial to the Drosophila learning mutants named for vegetables – turnip, cabbage, etc.
one of my favorite talks at the 2005 Society for Developmental Biology meeting in San Francisco was an early Drosophila patterning mutant called shaven baby – the presenter was French, so he pronounced it “sha-ven bebe.” yet by the end of the talk, the novelty was already gone.
Our good friends over at Expelled: The Movie must have registered the words ‘pz myers’ with adwords.
If you do a google search for ‘pz myers’ [1] their advertisement shows up at the top of the search results with the blurb “Creationism vs Evolution — Come see PZ Myers in the movie Expelled: No Intelligence Allowed”.
Now I’m no expert at how adworks works, but I think they have to pay each time you click on the link that shows up in the sponsored links (at top). A quick use of the ‘estimate keyword tool’ says it might cost them a whopping $0.05 (5 cents) for each click.
Anywho, I just thought it was kind of funny.
[1] http://www.google.com/search?q=pz+myers
The fly people pick the coolest gene names–zebrafish people don’t seem to have the edgy humor necessary to name their mutants with *flair*. Lame fishy examples include the gene ‘valentino’–the absence of which causes the normally bumpy and crenelated brain to appear smooth (valentino = smooth) another gene with a similar phenotype is named ‘casanova’.
The gene ‘sentinel’ was discovered in a screen for suppressors of neomycin-induced deafness (sentinel = something that opposes neo). Ugh.
This Evo-Devo meeting rocks. My brain is full.
Yes that is its full name. You see in Drosophila there is one gene, called Hedgehog after its mutant phenotype in embryos. While in mice there are more, often 4, due to genome duplications. Like there are 4 Hox clusters in mice vs 1 in Flies. So there is always a need for names for the mouse equivalents that reflect the origin, makes the associations easier to remember*. It gets fun, for eg Drosophpila fringe in the mouse becomes radical fringe and its fellow lunatic fringe ;-)
In the land of mouse hogs from the hedge there is desert hedgehog and tiggywinkle hedgehog (or is that the fish version? I forget)
*in C. elegans worms they are made to call genes by letters and numbers so all the associations are lost. Makes reading worm papers tedious.
Dammit, Peter, you stole all my anecdotes!
Small corrections – tiggywinkle is a hedgehog only found in fish (they have duplicates of lots of things because of a genome duplication at some point in their past). If I remember, the mamallian hedgehogs were sonic, desert and indian.
Also, there are three fringes in vertebrates – you forgot manic fringe!
Now the only fun one I have is the Notch ligand Serrate, whose orthologues are called Jagged to distinguish them. And that’s boring by comparison.
I had a lecturer who pointed out that the reverse-genetics approaches used to name genes like hedgehog (“the mutant is all spikey, like a hedgehog”; other genes in the pathway are called patched and smoothened, guess what their phenotypes were) was a bit backwards – you’re naming a gene on the basis of what happens when it breaks. She said it was a bit like calling a fridge a “milk souring device”.
I thought that I’d copy this here:
Darwin Was Right: Natural Selection Speeds Up Speciation
Download PDF of paper: Ecological Niche Dimensionality and the Evolutionary Diversification of Stick Insects.
I’d be interested to hear the thoughts of anyone who understands this in its proper context. I realize that this probably isn’t anything of great importance. Bloody hype!
Damian: in the original article, but not in the ScienceDaily piece, they are careful to point out that the ecotypes are not necessarily on their way to speciation. So it’s sort of circumstantial evidence – still good, but it’s not by far the first article to connect natural selection and (species/ecotype) divergence. However, the previous studies afaik didn’t use an experimental approach to confirm selection, so that justifies some of the excitement, I guess!
the reverse-genetics approaches used to name genes like hedgehog … was a bit backwards
This comes from the days before people knew what a gene is and does. “Gene” was defined as “the unit of heredity”, but the only thing the fly people had to work with was observable differences in the flies. They could tell by selective breeding that some differences were heritable, so they concluded that each difference was caused by a “gene”. Only later did geneticists begin to realize that many of these differences were caused by a gene that didn’t work.
WHAT!? PZ was here in Portland and there was no night out drinking planned? Damn!
You’ve missed out, I am afraid- we have more handcrafted beers per capita than the rest of the country combined. Well, maybe not, but, a lot, anyway.
Next time!