The evolution of deuterostome gastrulation


Do vertebrate embryos exhibit significant variation in their early development? Yes, they do—in particular, the earliest stages show distinct differences that mainly reflect differences in maternal investment and that cause significant distortions of early morphology during gastrulation. However, these earliest patterns represent workarounds, strategies to accommodate one variable (the amount of yolk in the egg), and the animals subsequently reorganize to put tissues into a canonical arrangement. Observations of gene expression during gastrulation are revealing deeper similarities that are common in all deuterostomes—not just vertebrates, but also the invertebrate chordates (tunicates and cephalochordates) and echinoderms.

What does all that mean? If you think of development as a formal dance, the earliest stages are like the prelude; everyone is getting out of their chairs around the ballroom, looking for partners and working their way towards the floor. The dispositions of the dancers are variable and somewhat chaotic, and vary from dance to dance. Once they get to their positions, however, we’re finding that not only is there a general similarity in their arrangements, but they’re all dancing to the very same tune. In this case, one of the repeated motifs in that tune is a gene, Nodal, which is active in gastrulation and shows a similar pattern in animal after animal.

Holoblastic cleavage of a sea urchin embryo

Let’s begin with the players beginning to take their places. There is much variation in how different deuterostomes carry out their earliest cell divisions, variation that we can reduce to two different categories: holoblastic vs. meroblastic cleavage.

Holoblastic cleavage is the easiest to visualize. The fertilized one-cell zygote divides completely into two separate cells, then each cell divides completely again to produce four cells, and again and again. The end result is a clustered mass of cells that resembles a bunch of grapes, or the druplets of a raspberry. This is the pattern of cleavage that we humans (and all mammals) use.

Meroblastic cleavage of a zebrafish embryo (the two partially separated cells are on top)

Meroblastic cleavages are incomplete divisions. The nuclei of the cell replicate and divide completely, but when cytokinesis (the actual division of the cytoplasm and membrane) occurs, only a partial membrane forms. This kind of division occurs in very yolky eggs, such as a chicken egg, and is a reasonable compromise to allow replication to occur rapidly by not bothering with the assembly of massive amounts of membrane. The yolk of a chicken egg is a single cell; imagine that having to be subdivided with new membranes at every division. Instead, the embryo typically forms as one small disc on the surface of the massive ball of yolk.

Holoblastic cleavage is almost certainly the ancestral condition, and is common in the invertebrate chordate phyla. Any animal that packs its eggs with lots of yolk, however, evolves the meroblastic shortcut at some point, and so a cladogram of the patterns of early cleavage looks rather chaotic—no nested hierarchies are easily visible here!

Cleavage patterns within the Chordates. Ascidians, lancelets, and lamprey display holoblastic cleavage, suggesting that it is the ancestral cleavage pattern in chordates. Ascidians have bilateral cleavage, while lancelets display radial cleavage. Lamprey and amphibians have meso-lecithal eggs, with larger, yolky cells confined to the vegetal half of the embryo. Present day teleost fish show meroblastic cleavage, which evolved independently in fish and amniotes. Mammals show a reversion to holoblastic cleavage, but exhibit rotational cleavage.

We can see the evolutionary relationships in other ways, though. Animals with meroblastic cleavage produce many cells, and eventually those cells migrate to engulf the uncleaved mass of the yolk. The cells that migrate eventually produce a thin membrane around it called the yolk sac. We mammals are a revealing example: from the cladogram, you’d predict that we had a reptilian ancestor that divided meroblastically, and that we secondarily lost that pattern of cleavage and readopted the ancestral holoblastic pattern as a consequence of not bothering to pack our eggs with yolk (instead, our eggs stay resident in women’s bodies and draw nourishment directly). Yet our zygotes still divide into many cells, and then a sub-population migrates to surround a fluid-filled, yolkless space—they make a yolk sac.

Out of the variability of the early divisions, however, comes order. The dance begins at gastrulation, when cells begin to make consistent patterns of migration to set up the layered tissues of the embryo. The milling masses of cells begin to line up and order themselves into a bilayered structure. In the diagrams below, you can see that most of the animals form a hollow ball, with one set of tissues above at the animal pole (a), and another set below at the vegetal pole (v). The animals with a more meroblastic cleavage tend to form discs instead of hollow balls, but it’s the same structure; the ball has just been flattened. The cell movements that follow consist of directed migrations towards the dorsal side, and invagination into the center of the hollow ball or disc that will produce a mesodermal layer.

Gastrulation in the deuterostomes. The animal pole (a) is marked by polar bodies; (v) is vegetal pole. (A) is future anterior; (P) is future posterior. In echinoderms and hemichordates, invagination of the endoderm begins at the vegetal pole and the early gastrula is radially symmetrical. The blastopore becomes the future anus of the larvae. In most echinoderms, the animal- vegetal axis becomes the larval A-P axis, except in echinoid and ophiuroid pluteus larvae. In chordates, invagination during gastrulation also begins at the vegetal pole. However, in the Chordata, the future anterior and posterior of the larva are determined by the point of sperm entry, which breaks the symmetry of the radial egg. The embryo posterior develops opposite the point of sperm entry.

Gastrulation is a complex process with many specific cell rearrangements and requiring the activation of many molecules. To keep things manageable, this paper focuses on one, nodal.

Nodal is a signaling molecule, a member of the TGF-β family, which plays a crucial role in gastrulation. In the middle diagram below, it is expressed as a graded signal which specifies where the Spemann organizer is to form—the organizer defines the site where the invagination of cells mentioned above is to occur, and is also a site where other molecules are expressed that signal migrating cells what position and fate they should take. Nodal is a central player in the formation and maintenance of mesoderm in early development.


Nodal is also a deuterostome universal: this molecule is used in similar ways cephalochordates, tunicates, echinoderms, and vertebrates. It has not been found in arthropods, although there are suggestions that polychaetes and molluscs may have a form of it. (All do have TFG-β molecules, just not the specific Nodal gene).

There is another critical function for nodal. It is later expressed in an asymmetric pattern, with a domain of expression on just one side. Slap your left side; it doesn’t matter whether you are left- or right-handed (although it does matter if you have situs inversus), you’ve found the side of your body where nodal was active when you were a little embryo. It’s also the same side where nodal was turned on in mice and frogs and fish and cephalochordates and tunicates, as you can see in the Late Gastrulation diagram below. It is also turned on asymmetrically in sea urchins, but it’s got a rather more complicated relationship to morphology there—it’s turned on in the region of the sea urchin’s prospective mouth.

Comparison of vertebrate nodal and nodal-related gene expression to lancelets, ascidians, and sea urchins. Animals are shown at early gastrulation (top, A–K) and after completion of gastrulation (bottom, B–L). Areas of nodal expression are indicated by heavy areas of shading. A: In mouse gastrulae, nodal is expressed bilaterally around the node. B: By early somite stages, nodal is expressed asymmetrically in the left lateral plate mesoderm and in the node where ingression is occurring. C: In early Xenopus gastrulae, nodal is expressed at the dorsal lip and later (D) in the left lateral plate mesoderm at late neurulation. E: Expression of cyc is localized to the hypoblast layer of the embryonic shield in early zebrafish embryos while sqt is expressed in the dorsal forerunner cells. F: During somitogenesis in zebrafish, cyc and spaw are both expressed in the left lateral plate mesoderm.
G: In lancelets, nodal expression is observed in the hypoblast layer of the dorsal lip. H: At late neurulation, nodal is asymmetrically expressed on the left side of the paraxial mesoderm, gut endoderm, and presumptive oral ectoderm. I: In ascidians, nodal is expressed bilaterally within the presumptive endoderm, epidermis, and trunk lateral cells from the 32-cell stage to early gastrulation. J: By the initial tailbud stage, ascidian nodal is expressed in the left side of the epidermis. K: In sea urchins, nodal expression begins in the presumptive ectoderm at the 60-cell stage, but decreases once gastrulation begins. L: Nodal transcripts are localized in the presumptive oral ectoderm during prism and pluteus stages.

The association with the echinoderm mouth is intriguing. In cephalochordates (the lancelet), the oral opening is initially asymmetric, too…and it forms on the left side. The authors suggest that one very interesting thing to examine would be the pattern of expression of nodal at the time the vertebrate mouth forms; it may have a role in that, too.

I’ve said a few things before about generating left-right asymmetries in development, and the key observation in us mammals at least is that the initial source of the asymmetry is the clockwise rotation of cilia on the surface of the node, the site of gastrulation. This rotation sets up a net leftward flow of fluids over the gastrula, which is illustrated below. In B, we’re looking at a cross-section of an embryo, with a couple of ciliary hairs sprouting up and spinning. At the same time, cells lining the surface are secreting nodal vesicular parcels (NVP), small membrane-bound blobs that contain a payload of signaling molecules, sonic hedgehog (shh) and retinoic acid (ra).

Breaking left-right symmetry at the node. A: A leftward fluid flow (indicated by arrows) is the earliest known asymmetric event in
mammalian left – right determination, resulting in activation of the nodal signaling cascade in the left lateral plate. In contrast in the chick, a
cascade of asymmetric gene expression at the node is upstream of the nodal signaling cascade. B: FGF signaling in the node permits
nodal vesicular parcel (NVP) production. Nodal flow carries NVPs to the left side of the node where they fragment, releasing lipid, SHH and
RA, activating left-sided Ca2+ signalling.

When the NVPs are released, they enter the bulk leftward flow, and are catapulted toward the left side of the embryo—when they contact the surface, they splatter apart, releasing their contents and triggering a signal cascade that eventual stimulates nodal expression. Now that is a Rube Goldberg machine, a weird way generate left-right differential expression of a gene.

As odd and unexpected as the mechanisms might be, the important message is that the deuterostome gastrulation dance seems to be choreographed in similar ways and with similar players. There are fascinating variations in individual species, though, and this molecule is a promising target for studies of the evolving regulation of development.

Chea HK, Wright CV, Swalla BJ (2005) Nodal signaling and the evolution of deuterostome gastrulation. Developmental Dynamics 234:269-278.

Norris D (2005) Breaking the left-right axis: do nodal parcels pass a signal to the left? Bioessays 27:991-994.


  1. says

    Now considering the email I sent Professor Myers was titled “asymmetry and the ecological crisis” — or to that effect — and that I sent the email just a couple days ago — I’d like to suggest it may have influenced the subject of this blog entry.

    On that note let’s proceed with what I recommended to Professor Myers and see if he is able to consider this top of asymmetry at an appropriate level of understanding.

    The cosmology book by astronomer Frank Close — The Lucifer Principle — details how asymmetry has been traced all the way back to the creation of neutrinos close to the Planck time limit of 10 to the minus 34 seconds or so. Asymmetry starts with the very beginning of the universe!

    “Nature has conspired against us” writes astronomer Frank Close.

    Nature has a left-hand directed asymmetry — through the now unified 3 fields of energy — weak, strong and electromagnetic.

    But gravity is the real puzzle because Newton got his inverse-square law by converting the previous foundation of Pythagorean resonance in water energy as intensity into iron-based density measurements.

    Newton realized that the intensity of the string is doubled by increasing the weight 4 times on the end of the string. Newton got his law of gravity directly from the Law of Pythagoras and Newton knew that Galileo and Bournelli were wrong when they attributed the Law of Pythagoras as an incorrect myth of hammer weight changing frequency.

    The problem with Newton’s law of gravity though is that it’s based on a logarithmic measurement which cuts off the alchemical resonance of energy. Newton was an alchemist above all else — which is why his shoulder-length hair was completely white by the age of 40: too much mercury.

    Anyway Pythagorean resonance is premised on no symbol for infinity — the nonlocal consciousness can not be contained by a Number and also Number resonates as complimentary opposites. The energy is based on the quantum properties of water as the Female principle — which is why Newton could not measure the cycles of the Moon properly and also why the Pythagoreans refused to bath in the communal Greek baths: water is too strong a conductor of energy as information.

    Hence the joke among the Greeks: “the dirty Pythagoreans.”

    Anyway when the ultraviolet catastrophe arose in the black box experiments of quantum mechanics science once again confronted the fact that energy intensity is tied to frequency — not to the amplitude as density vectors. The equipartition principle had been violated. Aristotelian logic no longer ruled. Science got psychedelic.

    The latest unified field science demonstrates that discrete numbers are really the basis for science and these discrete numbers are exactly the same alchemical numbers used by Pythagorean alchemists.

    The 5-D model of relativity uses discrete numbers (see astronomer Paul Wesson’s article in a recent New Scientist journal, posted on and is the most accurate demonstration of a unified field theory incorporating gravity.

    John Wheeler argues that black holes are governed by discrete numbers only — no real Number continuum — because “It comes from Bit.” Everything exists within a black hole.

    The new plasma energy technologies also utilize the discrete number information in lasers.

    Most importantly the Riemann Hypothesis — applicable to ALL ARENAS OF SCIENCE (just read “Stalking the Riemann Hypothesis) is based on discrete numbers.

    What does this have to do with asymmetry?

    Well science is converting left-hand directed carbon-based molecules into right-hand directed silica-based molecules through the nanotech revolution — all centered on the discrete number principles of the Bucky Ball and the Buckfullerene.

    The computers are in control (just as Professor Steve Strogatz, an expert in quantum chaos) — through discrete numbers — only the left-hand directed discrete number asymmetry of Nature is now reversed into a right-handed directed asymmetry.

    What causes this reversal? Well in quantum chaos terms it’s the “ghost resonance” of “hidden coherence” — the nonlocal consciousness of the formless 4th dimension of space.

    Silica is supposedly a symmetrical molecule but it is postulated that life evolved from right-hand directed asymmetrical crystallization of silica. Read Professor Cairn-Smith’s recent book “Evolving the Mind.” Or just google the topic.

    Right-hand directed asymmetry in the silica molecules are found in the brain — as Mad Cow Disease, as syphillis and increasingly as DNA-silica biochips.

    Silica-DNA biochips are THE technology of the future — just read “Nanotechnology and Homeland Security” (2005) — by the leading scientists in the field.

    Why is it that 96% of the universe is unknown — Dark Matter and Dark Energy? Read professor Michael Disney’s book “the Hidden Universe” — the Iceberg Effect is caused by the incorrect left-brain logic of phonetic axioms that created Western Civilizaton and ALSO created the ecological crisis.

    In otherwords the reason science can not understand the Cosmos is because it’s a reflection of the fact that humans are destroying left-hand directed carbon-based molecules on Earth.

    We have to really increasingly on the Artificial Life of the charge-coupled devices to give us an “accurate” reading of cosmology. But do those CCD’s really care about “science”?

    The water that makes up 60% of humans’ — our body and mind — is the pivot point for the transistion to the new right-hand directed silica-based molecules for Earth — through apocalyptic fire and metal technology.

    The water crisis is much worse than the oil crisis and water is the focus of new nanowater engineering at Sandia Labs. The new energy revolution is premised on nanowater.

    Just as NASA engineers — Dr. Robert Jastrow and the recent books “Privileged Planet” (endorsed by many top scientists) and “Biocosm” (by Yale-trained lawyer James Gardner and the book won a top science book of the year award by Discover magazine) —

    The Future of Evolution on Earth is right-hand directed silica-based molecules.

    drew hempel, MA

  2. Tom Hemsley says

    What kind cleavage happens in a platypus embryo? I have no clue how yolky the thing is but it does lay an egg.

  3. Josh says

    This blog is a rehash of an old blog entry sometime in 2005 (or somewhere around there), so don’t give yourself too much credit Drew. I suspect Prof Myers put this one in because he needs to keep up appearances while he’s away, and it’s an oldie but a goldie.
    By the way, did anything Drew say have anything to do with the blog entry by PZ?
    Still, thank you for showing us how clever you are

  4. Torbjörn Larsson says

    What is clever if not outright wrong in drew’s sciencebabble? They errors are too many, so a sampling must suffice:

    The amount of parity breaking in the universe is still unexplained. But so what? There are plenty of symmetry breaking that is still poorly understood.

    “the alchemical resonance of energy” doesn’t exist.

    “the ultraviolet catastrophe arose in the black box experiments of quantum mechanics” – Black body radiation can indeed be realised by using holes in boxes as sources. The rest is wrong. The ultraviolet catastrophe is classical theory and the absence of it is observed. That was the basis for the quanta idea that quantum mechanics grew out off.

    “the nonlocal consciousness” – nonnatural dualism.

    “Right-hand directed asymmetry in the silica molecules are found in the brain — as Mad Cow Disease, as syphillis and increasingly as DNA-silica biochips.”

    Prions and syfilis bacilla aren’t silica, neither are silicon biochips.

    “science is converting left-hand directed carbon-based molecules into right-hand directed silica-based molecules through the nanotech revolution” Of course science is doing no such thing. What is this obsession with silica? It has 17 crystal forms and several amorphous. What is the “right-hand directed silica” specifically?

    “Read professor Michael Disney’s book “the Hidden Universe” — the Iceberg Effect is caused by the incorrect left-brain logic of phonetic axioms that created Western Civilizaton and ALSO created the ecological crisis.”

    To argue that theories, formal or not, are constrained by some twist of our brains seems not well justified. It certainly isn’t related to parity breaking in the universe.

  5. Torbjörn Larsson says

    C-l-a-r-i-f-i-c-a-t-i-o-n. But I messed up your sarcasm, sorry about that. Not to clever of *me*.

  6. says

    Well I’m just hoping that You Torbjorn Larsson keep up with your reading of the journal Nature since it has featured at least two articles in the past 5 years on how silica from soybeans combined with prions is crucial to the construction on nanobiomotors.

    Also syphillis is caused by prions as well — well spirochetes with the wrong asymmetry — right-hand directed.

    In fact cancer it self has as its main cause the loss of the symmetrical tetrahedral geometry of the water molecules which then throws out of whack the time cycles of the mitrochondria.

    The crucial key here is the 4th dimension of space as the guiding nonlocal pilot wave of quantum chaos creating a universal form of life. These are different names for it:

    The twisted scroll ring (read “Sync” by professor Steve Strogatz)

    The Klein Bottle (read “Topologies of the Flesh” by professor emeritus Steven M. Rosen)

    The Double Torus (read Ralph Abraham’s quantum chaos books)

    The “cycloid-spiral spacetime motion” (read books on Victor Schauberger, the Austrian forester who designed plasma vortex aircraft for classified miltary projects in the U.S. and Germany)

    And there there’s the Buckyballs (read “Hacking Matter” a free online book on quantum dots and nanotech) — the equilateral Triangle is the MOST symmetric and therefore the MOST efficient transducer of energy.

    OK — I had a very close encounter with a totally flat, equilaterlateral black triangle aircraft.

    It was preceded by spheres of plasma doing inexplicable manuevers on the horizon — each sphere was a different color.

    That was summer of 1997. It was in a military test corridor which had a UFO flap in the 1970s and had cattle mutilation — so scary that the rancher adjacent to the state wildlife refuge moved out of the area.

    So science is much stranger than people give it credit. The Manhattan Project was bad enough.

    Positronium anti-matter technology — for propulsion and for vaporization — is top secret.

    Project HAARP — plasma laser transformation of the planet through extremely low frequency is top secret.

    Underground cities — top secret.

    Just the effects of depleted uranium are bad enough.

  7. Torbjörn Larsson says

    “Also syphillis is caused by prions as well — well spirochetes with the wrong asymmetry”

    Umpfh! Prions are proteins, spirochetes are bacilles.

    I’m afraid that we must do this in baby steps. Your world isn’t the world normally observed. Unless of course, you take the best approach as presented by Josh. More meds are strongly indicated.

  8. Scott Hatfield says


    OK, just out of curiousity I visited your web site. It’s filled with the same stuff that you put up here: at one moment making a sort of brilliant, albeit literary connection between two items that one wouldn’t ordinarily associate—in the next moment, a complete non sequitur, often accompanied by items from conspiracy theory.

    I want you to know I skimmed over your ‘master’s thesis’ as well. Same sort of thing. Just what was your degree supposed to be in? Was it granted? Was it…(shudder)…science? I don’t want to be mean, but surely you must realize that your attempts to communicate your ideas aren’t too successful. In cases like yours (which I’ve seen before), it’s not so much that you’re in need of medication, it’s that you’re addicted to your own cleverness. You have a real gift for making associations and you’ve used it to build an elaborate private belief system, and it’s got you in it’s hold. Kepler and Newton had similar commitments, but you know, they did manage to convey their ideas to the rest of the world.

    Here’s my advice. Try NOT thinking for awhile about the ideas that seem so vital to you. Try NOT reading other people’s ideas. Try to just experience life, and get in touch with the part of yourself that isn’t generating baroque complexity. You might be surprised.


  9. says

    Scott — have you tried googling my name “drew hempel”?

    I have posed as my virtual identities online. People have posted using my name for example.

    Do not be alarmed Scott — this is all for fun!

    As I stated I got the U of Minnesota to join the Workers Rights Consortium which entailed meeting 9 times over a year in very lengthy heated discussions.

    Before that I got the U of Minnesota to divest $1.5 million from a slave labor company.

    These achievements required strong social skills and the ability to endure intense psychological situations.

    For example the treasurer who supported my divestment measure and who told me she would do the same for tobacco stocks had her personal phone, files and email all infilitrated by the University Administration.

    So people who make a difference take a hit for it. She was fired.

    Scott I live a multi-faceted life that you might not be able to understand from a quick perusal of some of my writing.

    But I appreciate the attempt and I hope you have enjoyed yourself!

  10. says

    As for you Torbjörn I’m not cutting you any slack!

    Have you read Professor Brian Goodwin’s biology books — they’re the foundation for the digital biology revolution at M.I.T.!

    You’re just being reductionistic which is old-school thinking.

    New school thinking is taking Ones and Zeros and transforming codons into circuits.

    Neural networks, photonics, autoionized nanobiomotors.

    The future is Fresh and Exciting!

    I hope you patent yourself before some creepy scientist does it on the sly without you getting any cut.

    Oh but then you’re probably not “indigenous” will rare (valuable) traits.

    Yes I’ve exposed such nefarious research going on at the U of Minnesota and sure enough someone broke into their lab and stole their blood!

  11. Torbjörn Larsson says

    Keeping up with blogs during vacation is obviously too much for me – I have a life to keep up with too.

    I don’t think I am reductionistic. Can you exemplify? I think I am realistic.

    “New school thinking is taking Ones and Zeros and transforming codons into circuits.”

    Genetic codons aren’t about 0/1 and circuits.

    “Neural networks, photonics, autoionized nanobiomotors.”

    Neural networks needs a lot of modelling to solve problems. It is old school.