Evolution of sensory signaling

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How we sense the world has, ultimately, a cellular and molecular basis. We have these big brains that do amazingly sophisticated processing to interpret the flood of sensory information pouring in through our eyes, our skin, our ears, our noses…but when it gets right down to it, the proximate cause is the arrival of some chemical or mechanical or energetic stimulus at a cell, which then transforms the impact of the external world into ionic and electrical and chemical changes. This is a process called sensory signaling, or sensory signal transduction.

While we have multiple sensory modalities, with thousands of different specificities, many of them have a common core. We detect both light and odor (and our cells also sense neurotransmitters) with similar proteins: they use a family of G-protein-linked receptors. What that means is that the sensory stimulus is received by a receptor molecule specific for that stimulus, which then actives a G-protein on the intracellular side of the cell membrane, which in turn activates an effector enzyme that modifies the concentration of second messenger molecules in the cell. Receptors vary—you have a different receptor for each molecule you can smell. The effector enzymes vary—it can be adenylate cyclase, which changes the levels of cyclic AMP, or it can be phospholipase C, which generates other signalling molecules, DAG and IP3. The G-protein that links receptor and effector is the common element that unites a whole battery of senses. The evolutionary roots of our ability to see light and taste sugar are all tied together.

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And the Nobel goes to…

Andrew Fire and Craig Mello, for the discovery of RNAi. Read Pure Pedantry for an explanation for why this is important.

I’ll also mention that Carl Zimmer presents his take on this award…and wouldn’t you know it, evolution has its greasy fingerprints all over it.

I must also promote an excellent comment from Andy Groves:

I’ve said it before, and I’ll say it again for the benefit of ID supporters out there – this is what a real scientific revolution looks like. Fire and Mello published their paper in 1998 (two years after “Darwin’s Black Box” came out, for those who are interested). Since then, the number of primary research papers on RNAi, siRNAs and miRNAs stands at 12399, using the search terms

(RNAi OR siRNA OR miRNA) NOT review

12400 papers in eight years. That’s 1550 a year, or just over four papers a day. Would Bill Dembski, the Isaac Newton of information theory, care to comment?

Hmmm?

Every science paper, every bit of recognition given to working scientists, seems to be a rather nasty rebuke to the promulgators of creationism.

The Morris Café Scientifique lurches to life again!

Once again this year, I’m setting up our Café Scientifique-Morris, which is going to be held on the last Tuesday of each month of the university school year. This time around, that means the first one falls on…Halloween! So we’re going to do something fun for that one: maybe some costumes, lots of clips from classic horror movies, I definitely think we’re going to need some bubbling retorts of colored fluids, and the chemistry department is tentatively going to provide some treats (ice cream made with liquid nitrogen—chemistry and treats don’t usually go together in people’s heads, I know.) This is the announcement for the first talk:

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I’ve been ripping a few DVDs from my collection with classic portrayals of scientists—the Universal Frankenstein series, Re-animator, the Bond movies, etc. (any suggestions? Pass ’em on)—which show us off as evil villains, and I’m going to show short clips from them to illustrate our poor image. Then I’m going to follow up with more but less exciting clips of people like Sagan and Wilson and Dawkins and, if I can track it down, Bronowski to illustrate the real humanism of good scientists. Suggestions for the latter part are also welcome, and that will be the heart of the talk, but face it: I don’t want to overdo the moralizing, and all the fun is going to be in the monster-makers.

I’ve also finalized our schedule. I’ve opened it up to a few people on the other side of campus, so we’re also going to hear about the legal standards for the admission of scientific evidence, and the economics of alternative power generation and transmission, in addition to a discussion of the chemistry we all use in our homes, a bit of astronomy, and a session of insect identification.

  • 31 October 2006 :: PZ Myers, Biology
  • 28 November 2006 :: Theodora Economou, Law
  • 30 January 2007 :: Panel discussion, Chemistry
  • 27 February 2007 :: Arne Kildegaard, Economics
  • 27 March 2007 :: Kristin Kearns, Physics
  • 24 April 2007 :: Tracey Anderson, Biology

It’s looking like a good year for this seminar series. If you’re in the neighborhood, stop on by!

Hox complexity

Here’s a prediction for you: the image below is going to appear in a lot of textbooks in the near future.

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Confocal image of septuple in situ hybridization exhibiting the spatial expression of Hox gene transcripts in a developing Drosophila embryo. Stage 11 germband extended embryo (anterior to the left) is stained for labial (lab), Deformed (Dfd), Sex combs reduced (Scr), Antennapedia (Antp), Ultrabithorax (Ubx), abdominal-A (abd-A), Abdominal-B (Abd-B). Their orthologous relationships to vertebrate Hox homology groups are indicated below each gene.

That’s a technical tour-de-force: it’s a confocal image of a Drosophila embryo, stained with 7 fluorescent probes against different Hox genes. You can clearly see how they are laid out in order from the head end (at the left) to the tail end (which extends to the right, and then jackknifes over the top). Canonically, that order of expression along the body axis corresponds to the order of the genes in a cluster on the DNA, a property called colinearity. I’ve recently described work that shows that, in some organisms, colinearity breaks down. That colinearity seems to be a consequence of a primitive pattern of regulation that coupled the timing of development to the spatial arrangements of the tissues, and many organisms have evolved more sophisticated control of these patterning genes, making the old regulators obsolete…and allowing the clusters to break up without extreme consequences to the animal. A new review in Science by Lemons and McGinnis that surveys Hox gene clusters in different lineages shows that the control of the Hox genes is much, much more complicated than previously thought.

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Cellular responses to alcohol

Forgive me, but I’ll inflict a few more zebrafish videos on you. YouTube makes this fun and easy, and I’m going to be giving my students instruction in video micrography next week, so it’s good practice.

This is a more detailed look at what’s going on in the embryo. Using a 40x objective, we zoom in on a patch of cells near the surface of a 4-hour-old embryo—this is a generic tissue called the blastoderm. We just record activity with an 1800-fold time compression for a few hours to see what the cells are doing. The movie below displays typical, baseline activity: the cells are jostling about, you’ll see an occasional mitosis, and sometimes you’ll see a cell vanish out of focus as it moves deeper into the embryo, and sometimes you’ll suddenly see a new cell squirm to the surface. It’s all just a happy, dynamic place with lots of random motion; these can be mesmerizing to watch.

These blastoderm sheets are a kind of cellular testbed for quick assays of the effects of teratogens on embryonic tissues. We just wash the embryo with whatever substance we’re interested in testing, and see if and how the cells react.

Alcohol is a dramatic example. Here’s a blastoderm sheet under stress as it is exposed to 3% ethanol.

Some obvious changes are going on. One is that the surfaces of the individual cells are seething—they are bubbling out and sucking back in little balloons of membrane, a process called blebbing. This is a very typical response to any kind of stress. Apparently, mitosis is another kind of stress: we can reduce the concentration of alcohol so that the cells look normal, except that as they’re about to divide they go into a flurry of blebbing that persists until division is complete.

We had another puzzle to solve. Sometimes, as we were looking at our low magnification recordings of embryos, we’d see the whole blastula or gastrula shudder. They don’t have muscles yet! We didn’t know what was causing pulses of contractile activity to sweep across the whole animal at such a relatively undifferentiated stage.

These movies show what was going on. They’re a real pain to keep in focus, because in addition to the fine blebbing activity in individual cells, the whole surface occasionally dimples and changes shape. What’s happening? Cells are dying somewhat randomly, some on the surface, some deeper in the embryo. Deep cells that die seem to be actively evicted from interior; sometimes the surface will buckle inward (with the image going out of focus), and when it bounces back up, it ejects a load of cellular debris out into the external medium. There’s a particularly dramatic example at the end of this movie, where everything in the lower half goes massively out of focus, and when it bounces back, it carries a large dead cell that sits there briefly, then abruptly pops and disappears.

If you look at that earlier lower resolution movie of ethanol effects, you might notice odd rough blobs on the surface of the embryo, and we think what that is is the extruded debris of deep cells killed by alcohol exposure, thrown up out of the interior to prevent them from interfering with normal development. This is actually a rather cool cellular mechanism that helps embryos survive random glitches in the process of building these massive pools of cells as it grows—it’s a kind of tissue-level garbage disposal service.

Developing under the influence: zebrafish in alcohol

Ah, the evils of strong drink. Or weak drink. You all know that you shouldn’t drink alcohol to excess during pregnancy, and the reason is that it can affect fetal development. We take zebrafish eggs and put them on a real bender: we soak them in various concentrations of alcohol (which are hard to compare with human blood alcohol levels, I’m afraid, but trust me: these are such gross levels of ethanol that mere humans would be dead and pickled. Fish are tough), and let them stew for hours. Since fish development is much, much faster than human development, it’s rather like having a woman start drinking straight Everclear a few weeks after discovering she’s pregnant, and staying snockered throughout the first trimester.

So don’t try this at home, kids.

The animal on the left is a teetotaler control. The one on the right is going to get washed in 3% alcohol at about 4 hours of development. It’ll be obvious; a label will pop up, and also the eggs are embedded in agar to immobilize them, and the agar will go cloudy and dark for a while as the alcohol soaks in.

Even if you aren’t intimately familiar with fish embryology, you should be able to see that the one on the right develops more slowly. Especially at the end, the one on the left will be twitching vigorously and spinning in the chorion, while the lush on the right is much slower. There are also some subtle deformities in tail shape, and you might notice odd schmutzy gunk on the animal’s epidermis…more about that later.

Also, you’ll notice that we started both recordings immediately after fertilization—I was hovering over the tank, and as soon as momma and daddy squirted out the gametes, I scooped them up and slapped ’em down in a dish, to guarantee that everything was starting precisely in synchrony. These movies start a little earlier and go on a little longer than the previous example.

That zebrafish movie annotated and explained, a little

By popular request, here’s a roughly annotated version of that zebrafish development movie.

Stuff to watch for:

  • This movie starts at the 8-16 cell stage. The cells of the embryo proper (blastomeres) are at the top, sitting on a large yolk cell.

  • The pulsing is caused by the synchronous early divisions of all the cells. They lose synchrony at the mid-blastula transition.

  • Epiboly is the process by which the cells migrate downward over the yolk. An arrow will briefly flash, pointing to about 11:00, in the direction of the animal pole (where the future nose will form, sorta). That happens just before the whole animal begins to rotate within the chorion, just to make following everything more difficult.

  • After the animal rolls over, the animal pole is pointing straight up at you, and the migrating cells will form the germ ring, a thickening around the equator of the embryo. Cells will also migrate towards one point along the ring, forming a thickening called the keel. This is where the embryonic axis is forming; cells are migrating into the interior at this point in the process called gastrulation, and this region is roughly equivalent to the dorsal lip of a frog.

  • The whole animal is going to roll over again, this time to its side. The keel is thickening and lengthening towards the animal pole. The body of the fish is going to form along the right side of spherical embryo in this view.

  • While the keel is extending anteriorly, cells are still also migrating to surround the yolk—epiboly continues, with the yolk bulging out a bit until it is finally surrounded and closed off at the blastopore.

  • The head and tail extend. You’ll see the eye forming, so you’ll be able to tell which end is the head end.

  • Along the right side, you’ll also see the tissue form regular little blocks: these are the somites, or body segments.

  • The tail continues to extend and lifts off the surface of the yolk. When there are about 18 somites (the resolution is too low, so don’t try to count them), the animal will begin to twitch.

I’ll load up another one in a bit that will show a hint of the horrible stuff we do to them in the lab: we get the babies drunk and watch deformities develop.

How would ID have contributed?

Carl Zimmer brings up another essential point about the HAR1F study: it was work that was guided by evolutionary theory. The sequence would not have been recognized in the billions of nucleotides in the genome if it hadn’t been for an analysis directed by the principles of evolution.

Wells’ diatribe was amazingly wrong. I looked at it again and there could be another half-dozen essays in just picking up apart the stupidity in it.