Ready to Publish

Just sent this message off to editors of three journals.

Greetings,

Quick note to inquire about possible publication. Not sure if it would fit in any category in [journal]. Feel free to relay the below description to colleagues (or I would be grateful for ideas about alternative venues). I'm considering [journal] because this is where AC Clement published all his stuff, please read on...

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This is a story about a set of experiments whose results (published some years before you and I were born) established a very clear-cut model of body patterning - a model defined in terms of single-cell behaviors, not a molecular mechanism, but nonetheless well-defined. Combinatorial logic, along two orthogonal spatial axes, specifies single cells with about a dozen distinct organ-forming potentials in snail embryos. Something similar probably works in many other kinds of animals with spiral cleavage, but the logic was dissected in embryos of the sea snail Ilyanassa. This one guy, Anthony Clement, did all the work, reported in publications spanning over two decades starting in 1953 (finished posthumously in 1986). All Clement did was microsurgery to remove a single cell, then wait and see how the embryo turned out. He did this ablation on almost every single cell up to the 28-cell stage. Results were extremely reproducible. The model seems rock solid, now that clonal fate mapping has been done as well.

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(For my paper, I would have to first outline the model and briefly show & tell about its experimental basis.)

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An early step in this experimental analysis, published in 1956, was the isolation of half-embryos and quarter-embryos at the two-cell or four-cell stage. Results were mostly as predicted by the model in its present form. In the Discussion, Clement mentions having done other operations to produce three-quarter embryos, and promises these results to be published soon. Well... those results never were published.

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The surgery to create three-quarter embryos is just about the easiest thing to do to an embryo, so I started doing it. Mostly I got the results predicted by the beautiful model. But in a substantial fraction of cases (25% up to almost 50%) I got a different (and really weird) result, time after time. A result that seemed not to fit the model at all. Parts that should be developing, weren't. Meanwhile, parts that shouldn't be developing, were!

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Right away I suspected that Anthony Clement had decided to sweep these results under the rug. He couldn't figure out what was going on! As you'll see, it is complicated.

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Looking closer, I found that these aberrantly developing partial embryos were casting off their heads! Meanwhile, the lower part formed all its parts perfectly (and very surprisingly, since it supposedly lacked the proper founder cell identities).

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The cast-off heads were small vesicles - we might call them head organoids - swimming feebly around, looking undernourished, but with evident muscle and neural tissues. Usually with two eyes, but tiny eyes and spaced too closely together.

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I clocked the timing of head ejection, with a small margin of error. It corresponded to the stage when embryos normally begin elongating along the AP axis.

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I was growing single operated embryos in isolation. I noted that in head-ejecting embryos, a smattering of single cells was always to be found on the bottom of the well: some floating, some swimming, but mostly adhering to the glass. That's interesting too! Unfortunately I don't know anything more about those lost single cells. (Important to mention: in cases where development resulted in defects predicted by the beautiful model, single-cell escapes were never observed.)

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I developed a hypothesis to explain what's going on in this aberrant situation. In three-quarter embryos, I guess that sometimes blastomeres slip into an alternative configuration, such that 'ventral' ectoderm founder cells (which normally don't receive the signal from the Clement organizer cell 3D) are now exposed to the signal, and develop like the normal lateral cells. So they contribute to the shell and foot, and these body parts develop like normal. But without the normally specified 'ventral' cells, something's missing. Like in vertebrates, these cells' descendants normally spread out laterally, while dorsal and lateral regions converge and axially extend. The 'ventral' cells spread out so far to the sides, they wrap all the way around like a collar. It's literally the little snail's neck.

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OK, so what happens if you don't have a neck? Well, your head pops off. In the process, some cells at the broken interface are torn off or squirted out.

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This hypothesis makes predictions about what might result from a couple other single- or multiple-cell ablations, never reported. I did these too.

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An alternative hypothesis would be early signaling at the 4-cell stage, which is disrupted by removal of any one cell. I ruled that out.

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A straightforward prediction is seeing ERK activation in the wrong cells at organizer-signaling stage. Lacking a confocal microscope or sufficient attention energy, I wasn't able to check this out. I could have used an enzyme-linked antibody.

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So that's what I've got: a story that is extremely slender on mechanistic insight, but which presents an intriguing new way for things to go wrong. Heating up a cold case, exposing Clement's little secret, and trying reconcile the mystifying result with his lovely model. Whadaya think?

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Thanks in advance for your consideration.

~

Morgan Q Goulding

International Snail Station

EDIT: Less than 3 hours later, I am sitting here smiling like an imbecile - already got a positive response from one journal editor:):):)