Pharyngula

Snails have nodal!

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My first column in the Guardian science blog will be coming out soon, and it’s about a recent discovery that I found very exciting…but that some people may find strange and uninteresting. It’s all about the identification of nodal in snails.

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Why should we care? Well, nodal is a rather important — it’s a gene involved in the specification of left/right asymmetry in us chordates. You’re internally asymmetric in some important ways, with, for instance, a heart that is larger on the left than on the right. This is essential for robust physiological function — you’d be dead if you were internally symmetrical. It’s also consistent, with a few rare exceptions, that everyone has a stronger left ventricle than right. The way this is set up is by the activation of the cell signaling gene nodal on one side, the left. Nodal then activates other genes (like Pitx2) farther downstream, that leads to a bias in how development proceeds on the left vs. the right.

In us mammals, the way this asymmetry in gene expression seems to hinge on the way cilia rotate to set up a net leftward flow of extraembryonic fluids. This flow activates sensors on the left rather than the right, that upregulate nodal expression. So nodal is central to differential gene expression on left vs. right sides.

i-21bda85fe662c24fe34efc609dcbf4ac-nodal_cilia.jpg

What about snails? Snails are cool because their asymmetries are just hanging out there visibly, easy to see without taking a scalpel to their torsos (there are also internal asymmetries that we’d need to do a dissection to see, but the external markers are easier). The assymetries also appear very early in the embryo, in a process called spiral cleavage, and in the adult, they are obvious in the handedness of shell coiling. We can see shells with either a left-handed or right-handed spiral.

i-d03d89cba8e1ae44e04152b3d93bf105-nodal_spiral.jpeg
(Click for larger image)

Chirality in snails. a, Species with different chirality: sinistral
Busycon pulleyi (left) and dextral Fusinus salisbury (right). b, Sinistral (left)
and dextral (right) shells of Amphidromus perversus, a species with chiral
dimorphism. c, Early cleavage in dextral and sinistral species (based on ref.
27). In sinistral species, the third cleavage is in a counterclockwise direction,
but is clockwise in dextral species. In the next divisions the four quadrants
(A, B, C and D) are oriented as indicated. Cells coloured in yellow have an
endodermal fate and those in red have an endomesodermal fate in P. vulgata
(dextral)15 and B. glabrata (sinistral)28. L and R indicate left and right sides,
respectively. d, B. glabrata possesses a sinistral shell and sinistral cleavage
and internal organ organization. e, L. gigantea displays a dextral cleavage
pattern and internal organ organization, and a relatively flat shell
characteristic of limpets. Scale bars: a, 2.0 cm; b, 1.0 cm; d, 0.5 cm; e, 1.0 cm.

Until now, the only organisms thought to use nodal in setting up left/right asymmetries were us deuterostomes — chordates and echinoderms. In the other big (all right, bigger) branch of the animals, the protostomes, nodal seemed to be lacking. Little jellies, the cnidaria, didn’t have it, and one could argue that with radial symmetry it isn’t useful. The ecdysozoans, animals like insects and crustaceans and nematodes, which do show asymmetries, don’t use nodal for that function. This suggests that maybe nodal was a deuterostome innovation, something that was not used in setting up left and right in the last common ancestor of us animals.

That’s why this is interesting news. If a major protostome group, the lophotrochozoa (which includes the snails) use nodal to set up left and right, that implies that the ecdysozoans are the odd group — they secondarily lost nodal function. That would suggest then that our last common ancestor, a distant pre-Cambrian worm, used this molecule in the same way.

Look in the very early mollusc embryo, and there’s nodal (in red, below) switched on in one or a few cells on one side of the embryo, the right. It’s asymmetrical gene expression!

i-6daa81c2edebfc143fde371c4849c1cf-nodal_early_exp.jpeg
(Click for larger image)

Early expression of nodal and Pitx in snails. a, 32-cell stage L.
gigantea
expressing nodal in a single cell. b, Group of cells expressing Pitx in
L. gigantea. c, Onset of nodal expression in B. glabrata. d, A group of cells
expressing Pitx in B. glabrata. e, 32-cell L. gigantea expressing nodal (red) in
a single cell (2c) and brachyury (black) in two cells (3D and 3c).
f-h, brachyury (black) is expressed in a symmetrical manner in progeny of 3c
and 3d blastomeres (blue triangles in g), thus marking the bilateral axis, and
nodal (red) is expressed on the right side of L. gigantea in the progeny of 2c
and 1c blastomeres, as seen from the lateral (f) and posterior (g, h) views of
the same embryo. i, A group of cells expressing nodal (red) in the C quadrant
and Pitx (black) in the D quadrant of the 120-cell-stage embryo of L.
gigantea
. j, nodal (red) and Pitx (black) expression in adjacent areas of the
right lateral ectoderm in L. gigantea. L and R indicate the left and right sides
of the embryo, respectively. The black triangle in b and i, the green, yellow
and pink arrows in f and i, and the black and pink arrows in f and h point to
the equivalent cells. Scale bars: 50µm.

Seeing it expressed is tantalizing, but the next question is whether it actually does anything in these embryos. The test is to interfere with the nodal-Pitx2 pathway and see if the asymmetry goes away…and it does, in a dramatic way. There is a chemical inhibitor called SB-431542 that disrupts this pathway, and exposing embryos to it does interesting things to the formation of the shell. In the photos below, the animal on the left is a control, and what you’re seeing is a coiled shell (opening to the right). The other two views are of an animal treated with SB-431542…and look! Its shell doesn’t have either a left- or right-handed twist, and instead extends as a straight tube.

i-055b648d0eaf32f767e5cc31f9f9a19b-nodal_shell.jpeg
(Click for larger image)

Wild-type coiled and drug-treated non-coiled shells of B.
glabrata
.
Control animals
(e) display the normal sinistral shell morphology. Drug-treated animals
(f, g, exposed to SB-431542 from the 2-cell stage onwards) have straight
shells. f and g show an
individual, ethanol-fixed, and shown from the side (f) and slightly rotated
(g).

What this all means is that we’ve got a slightly better picture of what genes were present in the ancestral bilaterian animal. It probably had both nodal and Pitx2, and used them to build up handedness specializations. Grande and Patel spell this out:

Although Pitx orthologues have also been identified in non-deuterostomes such as Drosophila melanogaster and
Caenorhabditis elegans, in these species Pitx has not been reported in
asymmetrical expression patterns. Our results suggest that asymmetrical expression of Pitx might be an ancestral feature of the bilaterians.
Furthermore, our data suggest that nodal was present in the common
ancestor of all bilaterians and that it too may have been expressed
asymmetrically. Various lines of evidence indicate that the last common ancestor of all snails had a dextral body. If this is true, then our
data would suggest that this animal expressed both nodal and Pitx on
the right side. Combined with the fact that nodal and Pitx are also
expressed on the right side in sea urchins, this raises the possibility
that the bilaterian ancestor had left-right asymmetry controlled by
nodal and Pitx expressed on the right side of the body. Although
independent co-option is always a possibility, the hypotheses we present can be tested by examining nodal and Pitx expression and function in a variety of additional invertebrates.

It’s also, of course, more evidence for the unity of life. We are related to molluscs, and share key genes between us.


Grande C, Patel NH (2009) Nodal signalling is involved in left-right asymmetry in snails. Nature 457(7232):1007-11.

Comments

  1. #1 Brownian, OM
    April 13, 2009

    Awesome. I just did a bit on Hox genes and hedgehog homologues on a skeptical radio show I’m squatting on.

  2. #2 Nerd of Redhead, OM
    April 13, 2009

    Very intriguing how the commonality of the signaling genes goes way back into early history of animals. Just another piece of evidence in the huge mass of support for evolution.

  3. #3 Glen Davidson
    April 13, 2009

    It’s also, of course, more evidence for the unity of life. We are related to molluscs, and share key genes between us.

    But Dembski’s latest post has this title:

    In other words, phylogenetic reconstruction is sheer fantasy ?

    Surely a mathematician would know better than some mere biologist…

    Glen D
    http://tinyurl.com/6mb592

  4. #4 cervantes
    April 13, 2009

    Two questions or comments or whatever.

    1) Er, echinoderms are radially symmetric, nez pas? So why do they need it?
    2) Cnidarians aren’t protostomes, they’re diploblasts — they have no gut and no anus, nez pas? Presumably the protostomes and deuterostomes are more closely related to each other than they are to cnidarians.

    Details details . . .

  5. #5 The Tim Channel
    April 13, 2009

    This information is undoubtedly useful for solving all manner of ill that befalls us.

    It may also come in handy when designing custom built lifeforms.

    In the future, ID people will have a formula for identifying ‘God designed’ creatures from man-made ones. LOL.

    Enjoy.

  6. #6 'Tis Himself
    April 13, 2009

    As usual, a clear, concise explanation of an interesting aspect of biology. Thank you, PZ.

    We are related to molluscs, and share key genes between us.

    That’s no way to refer to my cousin. The more common “couch potato” is less insulting to molluscs.

  7. #7 JD
    April 13, 2009

    This is worthy of the Nodal Prize.

  8. #8 blf
    April 13, 2009

    I first read the title as Snails have noodles and was wondering why Pee Zed was posting recipes for Pasta Escargo (which is quite tasty!) as Peer-Reviewed Research. I still need to, ah, digest this article a bit more, but the first thing which occurs to is simple: If snails were previously thought to not have noodles, er, sorry, nodal, what was the explanation for the obvious asymmetry?

  9. #9 flaq
    April 13, 2009

    Really interesting.

    Completely off-topic, but this:

    The other two views are of an animal treated with SB-431542?and look! Its shell doesn’t have either a left- or right-handed twist, and instead extends as a straight tube.

    immediately made me think of when I was on the equator in Kenya and there was a man with a very simple roadside demonstration using a funnel and a bucket of water. A few meters north of the equator, the water spiraled out of the funnel in one direction; a few meters to the south it spiraled the other way. And if you stood right on the equator? Well, it did more or less the same thing as the poor little snail embryos with their non-spiraling tube shells: it poured straight out without spiraling at all.

  10. #10 rodiel
    April 13, 2009

    “Er, echinoderms are radially symmetric, nez pas? So why do they need it?”

    Only as adults… maybe that’s why.

  11. #11 blf
    April 13, 2009

    s/occurs to is simple/occurs to me is a simple question/

    Preview proofreading FAIL. Again. ;-( Sorry!

  12. #12 blf
    April 13, 2009

    flaq @9, http://www.badastronomy.com/bad/misc/coriolis.html

    The “demo” is an easily-done con.

  13. #13 Sili
    April 13, 2009

    How annoying to see that the sinistral snails have a ? embryolet (I don’t know the proper diminutive) rather than a ? one. But it was good to get reminded of how to asign handedness.

    Cervantes,

    I’m a great believer in simplified spelling, but I do believe it works better if you spell it “n’est-ce pas”.

  14. #14 MrProsser
    April 13, 2009

    flaq, I would recommend this page dealing with the Coriolis effect and the equator. Bad Coriolis Effect.

    It has much more to do about how they set it up than the Coriolis effect.

  15. #15 flaq
    April 13, 2009

    The “demo” is an easily-done con.

    Noooo! say it aint so. Ahh, crap. Well, at least now I know. Frak.

  16. #16 Pika
    April 13, 2009

    “…you’d be dead if you were internally symmetrical”

    What about Doctor Who? No, that can’t be true. That’s just crazy talk!

  17. #17 Uncephalized
    April 13, 2009

    Awesome! I love all the culture-war/poll-crashing stuff we do here, of course, but this kind of post is why I really started reading Pharyngula regularly in the first place. Peer-reviewed research FTW!

  18. #18 Hans Derycke
    April 13, 2009

    IHNTA,IJLTS spiral cleavage.

  19. #19 MrFire
    April 13, 2009

    I confess to being a member of that degenerate, illegitimate hack-fest known as organic chemistry, with little understanding in this area. But I must say it sounds beautiful. (Kind of like Shakespeare! No idea what that bastard is saying half the time.)

  20. #20 DaveH
    April 13, 2009

    In the link to situs inversus I finally found the answer to an old question of mine (thanks PZ). Two of my friends at school were twin brothers, one with inverted organs, blond, blue-eyed, tall and skinny; the other short, stocky, red hair, very dark brown eyes. The Wiki article suggests they may have been MONOzygotic. How cool is that?

  21. #21 octopod42
    April 13, 2009

    AWESOME.

    Now what does this say about heteromorph ammonites??

  22. #22 Stacy
    April 13, 2009

    Stupid question time … What is the simplest life form that we have identified that shares common genes? Is it bacteria? I’m guessing that’s the answer I’ll get – but I’m thinking more along the lines of an animal, maybe a worm??

    No laughing, OK? PZ just sparked my curiosity with this one.

  23. #23 Ulanda Ulucky, Air Traffic Control
    April 13, 2009

    I’m confused. Big Baby Jeebus was perfect, so he must have been symmetrical, but he was a human, so he must have been asymmetrical. Dear God the Bounty Hunter, why do you test me so?

  24. #24 SEF
    April 13, 2009

    Yay – snails!

    …_@o”

  25. #25 SAWells
    April 13, 2009

    @22: well, we have cytochrome C in common with all eukaryotes; that gets you to yeast. And we have DNA in common with everything*.

    *yes I know retroviruses go and complain to Abby.

  26. #26 malty
    April 13, 2009

    I’d like to see a photo of an adult snail with one of these straight shells. I can’t quite understand what I’m looking at in the example.

    On the other hand, this is one of a handful of PZ’s science posts that I really fully understood. He often loses me in the more complex genetic-lingo (or math, haha) so I’m pretty happy to be able to share in this with everyone!

  27. #27 Happy Tentacles
    April 13, 2009

    #16 & #23 Does this mean Doctor Who IS Jeebus? Makes sense. Though they might not like it when the Cathedrals are commandeered in the name of the Whovians.

  28. #28 2 cents
    April 13, 2009

    Hmmm…a possible future application in human genetic engineering: infuse a little SB-431542 in a developing embryo and – voila! – no more rightwingers. Gee, it might even prevent fundamentalism.

    *puts on mad scientist hat and dashs off to the lab*

  29. #29 AlgaeGirl
    April 13, 2009

    That’s pretty awesome! It’s great finding out I’m more closely related to distant relatives than I thought I was.

  30. #30 frog
    April 13, 2009

    PZ: It’s also, of course, more evidence for the unity of life.

    I’d say more evidence for the laziness of life. No matter how half-ass and rigged the solution, it’ll keep on being used rather than improved. Life only requires just good enough.

    So Saith Golem.

  31. #31 Newfie
    April 13, 2009

    Cephalopods and Snails in the same day? How ’bout some nutibranchs for the Monday Trifecta?

    / interesting story, btw. Thanks.

  32. #32 Monado
    April 13, 2009

    Thanks! I always wondered how some of the extinct nautiloids could have straight shells and some coiled. I think we now have a plausible hypothesis.

  33. #33 minusRusty
    April 13, 2009

    Science in the 21st century! Yay!

    -Rusty

  34. #34 Lord Zero
    April 13, 2009

    This is just beautiful. Marvelous indeed.
    May newer discoveries shatter the filogenetic
    tree harder ? I hopefully hope so.

    I just cant understand how people cant get
    how fantastic is to achieve new knowlenge
    about the world in which we live in.
    Do they lack curiosity ? Dont care a single
    bit ?

    Discoveries which further our understanding
    of life in such a way are fantastic.
    Im eager to see new papers related to this one.
    Ahhh, the sweet smell of new data coming in!

  35. #35 Steve_C
    April 13, 2009

    Does anyone remember the name or have bookmarked the post where PZ asked everyone to give their 2 sentence explanation of evolution. I can’t find it.

  36. #36 Stacy
    April 13, 2009

    @35 – Is this the one you are looking for?
    http://scienceblogs.com/pharyngula/2009/04/a_video_contest.php

  37. #37 tresmal
    April 13, 2009

    “…nodal and Pitx are also expressed on the right side in sea urchins,”
    Um, right side? In sea urchins?

  38. #38 Fred the Hun
    April 13, 2009

    “…nodal and Pitx are also expressed on the right side in sea urchins,”
    Um, right side? In sea urchins?

    Wild guess on my part since I’m not a biologist, but maybe it is evident in the blastula before it becomes penta radiate?

  39. #39 RossM
    April 13, 2009

    I assume plants are nodal too, as some twist to the left and some to the right (as Flanders and Swan sang many years ago). Or is this a different gene?

  40. #40 Alex Deam
    April 13, 2009

    My first column in the Guardian science blog will be coming out soon

    Uhhhh, indeterminate time period. I want to know now! Is this all part of you master plan to have us all frantically checking the Guardian every 30 seconds, PZ?

    Seriously, I was wondering when you were going to do your first article. Simon Singh seems to have had three bites of the cherry before you get your first (not that I’m complaining, he’s a great writer).

  41. #41 Ritchie Annand
    April 13, 2009

    #22: Genes for Hemoglobin. They’re astoundingly ancient, present in plants, bacteria, animals, etc.

    R. C. Hardison’s A brief history of hemoglobin has a nice little chart on the second page.

    There are probably more up to date charts since 1996, but I don’t know how to go about tracking them down.

  42. #42 Leukocyte
    April 14, 2009

    @12

    Wow, that blew my mind. I had heard about the Coriolis effect in sinks/toilets so many times that I had just taken it for truth.

    Why would a teacher offer such garbage to students when it is so easy to check? A trip to the school washroom (let alone the ones at home) will reveal drainage in both directions

    [hangs empirical-evidence-demanding head in shame]

  43. #43 Vasha
    April 14, 2009

    @Leukocyte:
    No reason to feel shamed. We all stuff our heads with so many bits of information that some of them never get examined at all. For years I’ve been going around confidently asserting that whereas bees inject their venom with a stinger, wasps do it with a bite. It was only very recently that someone replied, “Um, are you sure?” causing me to look it up, and find out that a) wasps do have a stinger, and b) their bite is not venomous. Oops! And my bit of misinformation has probably been filed away trustingly in the heads of some of the people I told it to, and will continue to propagate…

  44. #44 Peter Ashby
    April 14, 2009

    @Malty
    My bet is that the straight shelled embryos didn’t survive, remember snails have internal asymmetry as well so the treated ones would have symmetrical organs as well which is bad karma as PZ says.

    So snails have nodal, but do they have snail?

  45. #45 G. Tingey
    April 14, 2009

    I’d be careful about the Guardian.
    ( Sometimes known, for historical reasons as the: “Grauniad” )
    They have been known, quite arbitrarily to ban people, without discussion, for making factual and true criticisms of a particular religion (I’ll let you guess which one) under the entriely false accusation of “Racism”.

  46. #46 Kitty
    April 14, 2009

    I spent many years sifting out snail shells from soil samples to use as environmental indicators in archaeological contexts.
    I’m a dab hand at identifying them using just the apex of the shell. (Shell fragments without an apex cannot be counted).
    Occasionally I would get thrown when a shell which should have been dextral was sinistral but all other indicators were accurate.
    Thanks for explaining why. It’s bothered me for years.

    PS – There’s a huge experiment taking place in Europe over the next 6 months studying the changes in shell colour and markings of Cepaea spp (the banded snail). It’s aiming to get lots of people involved in recording the snails to show ‘Evolution in action’. Cepaea is among the most studied snails and there is a 60 year accumulation of data.
    Should be fun.

  47. #47 MadScientist
    April 14, 2009

    Wow – I didn’t realize snail shells came in left and right-hand spirals; I had the impression they were all left-hand as viewed from the vertex. I’ll be studying the snails more carefully now … when I see them.

    In a rather unique expression of left/right symmetry, I know these two brothers who are monozygotal twins; the parents happened to name one ‘Noel’ and the other ‘Leon’ (how’s that for a palindrome), one is left-handed and the other right-handed, one has his internal organs in the usual order and the other is a bit mixed up (heart more to the right rather than the left, etc). The brothers are chemists and known to some as the ‘chiral twins’. Their students may not realize that these guys have a mirror image twin though since they live on opposite sides of the planet. They’re both great guys though – no evil vs good twin in this case.

  48. #48 Libbie
    April 14, 2009

    This is so cool! I’ve always been fascinated by nodal. I work with birds, and birds display obvious asymmetry, too, with the bias being for the left side. Female birds have a vestigial reproductive tract on the right side with the left side being fully functional. I’ve always found this to be baffling and awesome.

    Thanks for the article, PZ!

  49. #49 bsa
    April 14, 2009

    Very cool; thanks, PZ for the post. If I had another lifetime and more brains, I would be a biologist just for the excitement of learning.

  50. #50 amphiox
    April 14, 2009

    Stacy #22:

    It depends on which genes you want to talk about. There are a substantial number of genes that are in fact shared by every single organism (thus far known at any rate) on earth. That is one of the lines of evidence that demonstrates that all surviving life descended from a universal common ancestor, which was probably not that different from some bacteria.

  51. #51 SEF
    April 14, 2009

    There’s a huge experiment taking place in Europe … to show ‘Evolution in action’.

    My banded snails are subject to a certain amount of very unnatural selection. I’m rather partial to them and have a tendency to acquire new ones when out blackberry-picking (they go into the bottom of the bucket with a leaf or two and then get added to the compost pile area of my garden when I retuen) or to rescue them from dangerous situations, such as nearby footpaths. So it’s something of an advantage for them to be visible rather than extremely well camouflaged.

  52. #52 Alex Deam
    April 14, 2009

    I’d be careful about the Guardian.
    ( Sometimes known, for historical reasons as the: “Grauniad” )
    They have been known, quite arbitrarily to ban people, without discussion, for making factual and true criticisms of a particular religion (I’ll let you guess which one) under the entriely false accusation of “Racism”.

    Considering that one of their most prominent columnists is Polly Toynbee, an atheist, who every now and again will do a column criticizing religions (particularly the big three), then I think the Guardian is ok with publishing criticism of religion. Clearly they have a line where such criticism becomes racism in their opinion or at least could be deemed racism by someone, but clearly they still allow criticism.

  53. #53 tmaxPA
    April 14, 2009

    I’m always amazed how we can learn more in an evening than all of the authors of all the Holy Books ever written ever learned in all their lives about this fascinating world.

    Which also reminds me of a moment worth a callback. I am even more truly amazed when someone can sit in front of their computer and type things which question the validity of materialist reductionism. Or, as the phrase went previously, “methodological naturalism”.

  54. #54 astrounit
    April 15, 2009

    This is fantastically beautiful.

    The intrigue built up like a charge as I read on and finally struck me like a thunderclap. Seeing how the SB-431542 inhibits the nodal-Pitx pathway to produce symmetrically straight-shelled development was electrying enough, but the idea that the nodal/Pitx gene-expression for asymmetry evolved once symmetrical bilaterian physiology emerged to be thus exploited – that is the brightest bolt I’ve seen in a long time.

    Yet another splendid example of cumulative natural selection: “Although independent co-option is always a possibility” as the authors caution, symmetry laid the ground for it’s expression – having two sides carries a vast latent potential for handedness. One (asymmetry) comes AFTER the other (bilateral symmetry) is established. Symmetry sets the stage for asymmetry, and the constant mutational tinkering assures that the expression of asymmetry is spontaneous and inevitable.

    Evidence for unity of life, evolution by cumulative selection, shell “screwiness” and the handedness mystery all brilliantly illuminated by a single bolt. Awesome. My new favorite.

    More please.

  55. #55 Vian
    December 15, 2009

    nc knwlg

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