Sir, [sent to Dr Stuart Edelstein]

I contact you on your quality of Editor-in-Chief of Comptes Rendus Biologies. I would be grateful if you forward this message to your colleague Dr Rosa, who’s e-mail address I was unable to find and eventually to any other person more appropriate to deal with the issue I’m presenting below.

Almost three weeks ago was announced the corrected proof of an article by Vincent Fleury, titled « Dynamic topology of the cephalochordate to amniote morphological transition: A self-organized system of Russian dolls », released as doi: 10.1016/j.crvi.2010.11.009, accepted for publication by your journal, Comptes Rendus Biologies.

I dare suggest a more advanced review process is necessary before letting the article go to print and point below to a few problems I grasped over a reading. Of course, my remarks, if you consider them as pertinent, would need confirmation by experts of the field, despite the fact that a few ones originate directly to embryology textbooks.

For full disclosure, I have in the past had several exchanges with the author concerning his views of evolutionary biology and I’m a virulent critic of his point of view about the subject:

http://tinyurl.com/vfbspf: Vekris : the antero-posterior construction of animals is bullshit, the induction of limbs by genes is bullshit, the colinearity of hox genes is bullshit, the selection of tetrapods by evolution is bullshit, the duplication of genes between hindlimbs and forelimbs is bullshit

Of course I don’t consider biology to be bullshit. And I’m accustomed to the low quality of Dr Fleury’s manuscripts and the absence of willingness to improve them when errors are clearly documented, this is why I’m addressing you directly.

A few remarks about the present article.


During evolution of vertebrates a sequence of events is empirically observed: first, animals are bilateral, but they have no heart, no head, and no surrounding bag during development (these primitive animals are called cephalochordates [1]).

The introductory phrase wrongly class cephalochordates between vertebrates and falsely introduce the notion of absence of a « head » in Cephalochordates.

The notion of « more evolved » animals comes with no proper definition as the mention of chronology, vaguely termed « next ». It is absent from modern biological evolution theory and even the reference to Darwin’s Origin is vague with no proper reference to a particular statement of the author.

Morulae are described as round or discoidal shell of cells ; as the name indicates, morulas are globular, mulberry like.

The author from the single study of avian gastrulation generalize over two subphyla (cephalochordata and vertebrata) without providing any comparison between their developmental stages, not even for the diverse gastrulation processes, gastrulation being the stage standing at the basis of his thesisー within the Vertebrata subphylum, gastrulation differs between Amphibia, Aves, Mammalia and Osteichthyes.

3. Heart formation

The author claim that:

The origin of the heart is often described in terms of presence of a predetermined « cardiac territory » or « cardiogenic plate » [4,5], a concept which has little explanatory power from a physical, mechanistic, point of view.

The precardiac areas and the formation of the heart in several types of amniotic embryos are very well described and several resources can instruct who is interested by the process. Cardiac progenitors have being tracked from pre-streack HH 1 stage to the formation of the primary heart field at stage HH 4-5, then through HH8 and HH9 which are depicted in the animations provided by the author. (Reference guide to the stages of chick heart embryology, Brad J. Martinsen doi: 10.1002/dvdy.20468)

One can reach detailed information in the early scientific literature concerning The precardiac areas and formation of the tubular heart in the chick embryo (Helge Stalsberg & Robert L. DeHaan, 1969, doi:10.1016/0012-1606(69)90052-9) from early studies, or get a more recent review of the subject and of the adjustments of the Concepts of Cardiac Development in Retrospect (Gert van den Berg & Antoon F. M. Moorman, 2009, doi: 10.1007/s00246-008-9369-). And pictorial reviews of the heart formation are available at resolutions higher than the author offers, e.g. by Jörg Männer: Cardiac looping in the chick embryo: A morphological review with special reference to terminological and biomechanical aspects of the looping process, 2000, doi: <a href="http://dx.doi.org/10.1002/1097-0185(20000701)259:33.0.CO;2-K »>10.1002/1097-0185(20000701)259:33.0.CO;2-K

Along with the anatomical studies, molecular pathways leading to Embryonic Heart Induction (doi:10.1196/annals.1380.008 have being explored and catalogs of mutations affecting cardiac formation and function are available for model organisms.

Maybe the data are not satisfactory from a physical point of view and for the particular physicist, but one can not ignore them when proposing a new model, at least not those directly contradicting it and contrasting with the descriptions he make of the system under study. And the proposed model isn’t satisfactory from a physical point of view neither.

The author postulates a bending of tissues, due to the anteroposterior expansion of tissues along the central axis of the embryo, which would determine the « cardiac fold », oriented ventrally. Then he postulates the existence of a caudal « cardiac fold » supposedly forming the caudal heart in the hagfish, necessary for his view of a anteroposterior mirror symmetry.

There is no evidence presented about the contribution of the postulated « cardiac fold » in the formation of the caudal heart of the hagfish. The work of D. Jensen is referenced in the article as evidence of the existence of caudal hearts, which is used as an argument to postulate a caudal « cardial fold ». From Jensen’s description (page 447 of ref 8, doi: 10.1111/j.1749-6632.1965.tb49418.x):

Situated in the caudal region are a pair of flattened sacs between which lies a cartilagenous plate. Lateral bending of this cartilagenous plate by rhythmic contractions of those skeletal muscles which are attached to it causes alternate filling and emptying of the lateral sacs: thus, the caudal heart propels the blood forward from the large subcutaneous sinuses, as the hagfish circulation is partly open. Retrograde flow is prevented by valves. Incidentally, the caudal heart is innervated, and its intermittent rhythmic beat is initiated by impulses from the central nervous system

The author erroneously describe the caudal heart of the hagfish as aneural, one wonders if he read the article in reference. The caudal heart is formed by the juxtaposition of two caudal veins, without any particular bending in the direction proposed by the author. There is no evidence in the proposed reference to support the authors claim. As far as we know there is no evidence at all in the literature to support the claim of a caudal « cardiac fold ».

The same kind of juxtaposition along the anteroposterior axis is observed during the formation of the chick’s heart where two cardiac tubes, formed laterally, come together, parallel to the anteroposterior axis and fuse to form the tubular heart. At each side of the embryo, two vessels are produced in early stages from the primary heart fields, parallel to the anteroposterior axis. The embryos folding around an axis parallel to the anteroposterior one, bring together the distal vessels corresponding to the future endocardial tubes, which will fuse to form the tubular heart, and the medial ones are displaced dorsally, where they will form the dorsal aortas. The author seem oblivious to this embryonic fold which is essential for the heart formation. It is better understood from the observation of coronal sections of the embryo and a nice illustration can be found in the Reference Guide to the Stages of Chick HeartEmbryology, fig 3.2 reproduced below (Brad J. Martinsen, 2005, doi: 10.1002/dvdy.20468):

Capture d’écran 2011-01-27 à 09.58.49.png

This is the primary fold necessary to bring together the tissues that will form the tubular heart, which lies parallel to the anteroposterior axis.

The direction of the « cardiac folding » as described by the author, be it just for the anterior one, described as perpendicular to the anteroposterior axis, would be in competition with the observed tissues movements, cumbersome to the endocardial tubes fusion and the myocardium formation.
The proposed model is disconnected from data issued from more detailed observations, widely available and part of standard syllabus of embryology for undergrad students.

4. Chorion formation

What is termed erroneously « chorion formation » seems to correspond to the amnios formation, the author being oblivious to the omnidirectional development of the chorion which finally englobe every other tissue in the egg, with the ventral to the embryo part developing earlier and faster than the amniotic folds.

Amniotic folds are correctly described as progressing omnidirectionaly to form a closure dorsally to the embryo, where the chorion and the amnios will separate, in the terms of the author: « constrict again like a purse ». There is no physical, mechanistic, justification of why only the perpendicular to the anteroposterior axis component is discussed and not those almost parallel to it, clearly visible in the microphotographs of fig. 5.

While the author acknowledge that the occurrence of the two amniotic folds is temporally dissociated, the anterior one (HH 9+ to 10-) preceding the posterior one (HH 16), there is no physical, mechanistic, explanations of what would cause such a difference if the amniotic folds were initiated by mechanical forces due to the anteroposterior extension of the embryo. Or how the « ventral » extension of the chorion would be initiated. Fig 4b of the paper, where the to « chorionic folds » are represented on the same schema is misleading impression of simultaneity and symmetry contrary to the clarity claimed by the author, independently of the presence of the « caudal cardial fold » which comes without any documentation.

5. Origin of the heart and chorionic folds

Contrary to the claim of the author:

As we have seen, the dynamics and the topology of heart and chorion formation are similar.

the dynamics and topology of heart and « chorion » (as for amnios) formation are quite dissimilar of what is known, not only from the scientific literature but also embryology textbooks ; there is much more detailed and pertinent descriptions than the ones provided by the author.

To summarize

The author use in a quite inappropriate way standard vocabulary to describe embryonic features.

Claim the existence of a « caudal cardiac fold » mislead by the existence of blood draining features in the hagfish, termed caudal heart, which do not require any « caudal fold » as the one claimed, to develop.

From an incomplete understanding of the hagfish circulatory system, focusing only to the systemic and caudal heart, letting aside the cephalic and portal ones, he concludes to a mirror symmetry of the circulatory system, which he abusively transpose to the amniote embryo development.

The author seems oblivious of the dynamics of heart development and even of the embryonic folding around an axis situated ventrally and parallel to the neural fold, which forms the foregut/larunx and also participates to bring together the endocardial tubes and help the formation of the myocardium.

I don’t dare imagine that a biologist, much less an embryologist, reviewed the manuscript prior to acceptance for publication. I don’t even understand how a review by a physicist wouldn’t have asked for an explanation for the asynchronous appearance of the anterior and posterior amniotic folds if they were due to a single mechanical cause.
I am far from being an embryologists myself, and while my knowledge of chicken embryology have being improved in contrast to the authors claims in previously published articles, I propose that you get more insightful and expert comments from an embryologist, a specialist of the domain, Brad Martinsen is the first name that comes in mind. Prior to letting this article go to print. And probably the review by a specialist of the heart evolution would not be inappropriate, Mike Levine or one of his collaborators, more focused on heart evolution, may be willing to review it.

Brad J. Martinsen, Department of Pediatrics, Division of Pediatric Cardiology, University of Minnesota School of Medicine, Minneapolis, MN 55455. E-mail: marti198@umn.edu

Michael Levine,Levine Lab, University of California, Berkeley, Department of Molecular & Cell Biology, 42 Life Sciences Addition # 3200, Berkeley, CA 94720-3200 Email Address: mlevine@berkeley.edu

  1. Clarifying tetrapod embryogenesis, accurately | Coffee and Sci(ence)

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