Quite clear

This is an excerpt from Flery’s paper, p16, column 1.

However, Popperl et al.’s article deals mostly with the role of lazarus in the cranial (hindbrain and anterior trunk) compartment, (especially it shows how pbx genes participate in the regulatory loop of hox genes needed to specify rhombomere boundaries in the hindbrain) and when coming to limbs gives the same evidence that Tbx5 triggers forelimb outgrowth, since lzr-/- zebrafish do not show fin rudiments at all, and no Tbx5 staining. There is no rationale about limb positioning, apart from a correlation between absence of lazarus, and absence of fins. Especially, it is quite clear that the fin rudiments appear as round balls on the side of the flanks (Fig. 6. I in Ref. [80]). No mechanistic explanation is given of how a collinear series of genes along the neural crest might induce lateral formation of roundish masses of cells (the fin precursor). Popperl’s et al. article deals with deletion of hoxb-5 and hoxb-6 genes, and shows only a very modest shift of the shoulder girdle of about one or at most two vertebrae, when hoxb-5 genes are deleted and no mechanistic explanation. It is difficult to understand from this work in what respect hoxb-5 might be related to limb “positioning”, since when totally absent, there is a normal limb, which is “positioned” by something, and the position is almost normal, except that it is slightly shifted from the wild type.

It discuss material from “Lazarus Is a Novel pbx Gene that Globally Mediates hox Gene Function in Zebrafish”, a paper authored by Heike Pöpperl, Holly Rikhof, Heather Cheng, Pascal Haffter, Charles B. Kimmel and Cecilia B. Moens, and published in Molecular Cell, Volume 6, Issue 2, August 2000, Pages 255-267, doi:10.1016/S1097-2765(00)00027-7.



Well, first thing to clarify is that Popperl’s et al. paper do not deal with deletion of hoxb-5 and hoxb-6 genes; they are not even mentioned in the paper! So, it is not just “difficult to understand from this work in what respect hoxb-5 might be related to limb “positioning”“, it is impossible.

It’s the paper “Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation”, authored by Rancourt DE, Tsuzuki T and Capecchi MR, published in Genes Dev. 1995 Jan 1;9(1):108-22 doi:10.1101/gad.9.1.108 that deals with hoxb-5 and hoxb-6 deletion in mice, showing homeotic transformations of the cervicothoracix vertebrae from C6 to T1 common to both hoxb-5 and hoxb-6 homozygotes, and a rostral shift of the shoulder girdle for hoxb-5 homozygotes.

It would have be wise to consider a more recent paper reporting simultaneous deletions of the four hox5 (and others) genes (10.1242/dev.007567).
That was the first thing and it’s just a mere Oops! and a pointer to an inadequate bibliographic choice.


Second thing to clarify: “There is no rationale about limb positioning, apart from a correlation between absence of lazarus, and absence of fins.“. No lazarus, no fin buds. That’s not a correlation, that’s a causal relation. It may be direct or (more probably) indirect but it stays a causal relation. And whatever the mechanism that impairs fin buds development is, it remains a causal relation. No lazarus, no fin buds. Very much like no electrical current, no magnetic field in your electromagnet. Quite easy to understand.
But Vincent Fleury is quite a skeptic, who avoid to rely on empirical evidence and apply critical thinking in front of experimental results4.


Third and last and mind-blowing thing to clarify, the presence of “fin rudiments appear[ing] as round balls on the side of the flanks (Fig. 6. I in Ref. [80])“.

Let’s have a lateral view of a zebrafish embryo1

wtzemulti.jpg

Wild-type embryo (wt) analysed with a combination of probes that label, from anterior to posterior, forebrain (six3), the midbrain–hindbrain boundary (fgf-8), hindbrain rhombomeres 3 and 5 ( Krox20, k20, stars), spinal cord (HoxC8) and somites (s, fgf8 and HoxC8).

Just to have an overview of the embryo and the distance between the first somite from the rhobomeres 6/7 of the hindbrain.

Now, let’s have a close look at Fig. 6. I in Ref. [80] and the “round balls“:

hoxb36I_80.jpg

Wild-type, dorsal view with anterior to the left, with arrowhead indicating the r3/4 boundary, hox (blue) and krox20 (red) double in situ

All I could think of as “round balls” is the hoxb3 expression domains adjacent to rhobomeres 5-6-7. At the hindbrain level. Fucking2 fin buds at the hindbrain level! Quite clear! It’s just impossible to see the fin buds in this image. And this is a fucking wild type embryo, anyway.

Seems like the best factors to displace fin buds are ignorance and ill-informed imagination and it’s indeed quite clear that Fleury dispose of what is required to displace fin buds at the hindbrain level.
And it’s also quite clear the the review process of EPJ AP sucks3, at least when it comes to developmental biology; maybe they should avoid the subject in the future and redirect evodevo related papers to specialized journals.


1. Activin- and Nodal-related factors control antero–posterior patterning of the zebrafish embryo, Bernard Thisse, Christopher V. E. Wright and Christine Thisse, Nature 403, 425-428(27 January 2000) doi:10.1038/35000200, figure 2, panel “a”
2. If you find offending the use of “fucking” in this paper review, just think about how offending is the text of Vincent Fleury.
3. I was thinking that they had a reputation to sustain, and checked for their impact factor [pdf]: 0.938 in the Applied Physics Category. Well, I don’t think our physicist’s point of view will help them to improve.
4.
Je prends les travaux qui existent, et je réfléchis dessus, au lieu de tout gober sans esprit critique.

[Source, FAQ12]

6 Responses

  1. Are you going to check every single reference?

  2. Probably🙂

  3. you should add a direct link for the fig 6. I, even if you have to copy it on the light side of the paywall

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