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.


  1. JoeB says

    Really fascinating stuff. The blebbing especially is something that I just had no idea about before.

    Any ideas as to how the embryo can actively expel this cell without muscles?

  2. says

    Cells are motile and can vary their adhesive properties, so I expect there must be some local shifts in cell:cell interactions that coordinate this kind of reaction. If dying cells simply lose their adhesion to their neighbors, they could be squeezed out fairly trivially.

  3. plunge says

    Your fish are an abomintion unto the Lord! And I bet they’re really fun at parties too.

    Question: is the mechanism for dying cells losing their adhesion the general case for cells dying even in adult bodies? And are the external structures that control adhesion in any way related to what an immune system looks for as markers for all its various purposes?

  4. says

    > Any ideas as to how the embryo can actively expel this cell without muscles?

    Obviously evilutionists cannot explain this. The answer is obvious: they were designed to do it! Or alternatively, God simply did it.

  5. RobertD2 says

    I’m just a bad person. I read the title of this post and my first thought was of inappropriate late-nite/early morning calls I have made outside of noisy clubs….

    Really enjoy your blog Dr. Myers.
    I’m an engineer and a physics kind of guy so I it’s a lot of fun just trying to keep up with the science part of it. Have to admit, I don’t always make it.

  6. lo says

    Just wanna be frank, i`ve seen better but they certainly range in the middle as far as quality goes (the compression aside).

    Anyway how does embryogenesis react to kinetic forces (e.g. constant shaking/numerous shakings). I am fine with an educated guess – which is enough to point me in the right direction. At some point, when the external forces acting become too great no functional organism can be produced even to the stage of gastrulation, or am i misled? (please anyone throw some keywords at me, coz my searches have been in vein thus far)

    And do you know anyone who could put up videos of embryogenesis under microgravity / hypergravity conditions. I`ve read a dozen of studies but not seen a video once. I`d do fine with an animation as well.
    Damn i wish searching for specific multimedia files would be easier, but it isn`t and prolly won`t for quite some time. I know it`s out there but the search has been an unwavering PITA.

    PS:@PZ, I think it`s great what you`re doing recently and admire that!