Sunday, April 21, 2013

How Snakes Lost Their Legs



Have you ever wondered why snakes have no limbs? Research in the U.K. may be able to shed some light on this age old question. Evidence taken from the fossil record has long shown that the ancestor of snakes possessed limbs like modern lizards. Limb loss in snakes is thought to have been caused by changes in expression of several “toolkit” genes during development.  Alterations in these gene networks prevent formation of the forelimb and hindlimbs during development in snake embryos. One of the families of genes affected are Hox genes. In almost all animals, the overall body plan is based on a pattern of repeated segmentation along the anterior/posterior axis. Just think of vertebrae in chordates or body segments in insects. Combinations of Hox genes expressed along the anterior/posterior axis determine the identity of the different segments. For example, Hox gene expression boundaries determine the placement of the wing segments, antenna segments, and abdominal segments in fruit flies. Consequently, changing the expression patterns of Hox genes can cause aberrations, such as a fruit fly growing legs out of it’s head.

The researchers in this study looked at the expression patterns of the Hox genes HoxC6, HoxC8, and HoxB5 in python embryos. In other tetrapods and fish, the anterior expression boundaries of these proteins specify placement of forelimb developmental fields. In snakes, the anterior expression boundaries of HoxC8 and HoxB5 are shifted more anterior as compared to other tetrapods, which seems to completely eliminate the python’s ability to generate forelimbs. In contrast, these python embryos had normal posterior expression boundaries of these genes as compared to other tetrapods. This is consistent with existing morphological information. In ancient species of snakes such as pythons and boa constrictors, elimination of the hindlimb developmental field is not as complete as the forelimb field. Pythons actually do posses small outgrowths near the end of their bodies that are vestigial structures left over from when they possessed fully formed hindlimbs (Fig.1). This indicates that separate mechanisms are responsible for loss of the hindlimbs as compared to the forelimbs, and maybe even that the developmental programs necessary to specify hindlimb outgrowth in pythons are still present. The researchers set out to test this. Outgrowth of limbs depends on a layer of embryonic tissue known as the apical ectodermal ridge (AER) and a set of genes including fgf2 and msx that are normally expressed in it. Upon examination, the researchers found no evidence of an AER or the associated genes in python embryos. This could explain the lack of hindlimb development in pythons. In other organisms, fibroblast growth factors (fgfs) are responsible for formation of an AER. The researchers tested whether they could induce AER formation in python embryos by grafting fgf2 laced beads into the embryos. One day after grafting, this resulted in a 31% increase in hindlimb bud outgrowth in these python embryos, indicating that fgf signaling can induce hindlimb formation in pythons.


                                         Fig.1: spurs on python tail, vestigial structures left over from hindlimbs

The findings of these researchers illustrate a common trend that is emerging in the new field of evolutionary developmental biology, or evo-devo, which seeks to determine the developmental genetic mechanisms that underlie evolutionary change. Large changes in organismic morphology can occur through changes in a small number of developmentally important genes. This principle is shown by the ability to partially rescue growth of hindlimbs in python embryos by introduction of a single gene. Another important finding in this field is that the developmental programs necessary to generate novel morphological structures are often present in organisms that don’t even yet have those structures. For example, the pythons in this study maintained all of the genetic machinery necessary to develop hindlimbs. All they needed was the right genetic switch at the right place and time in developmental to kick off the whole program. And just like that, you get a snake with legs.

Posted by Sean McDougall (2)

11 comments:

  1. Even though snakes have "lost their limbs", they still have a fully functional pelvic girdle, with the bones necessary for limbs (i.e. a decent enough femur and functional too!). Also, a few weeks ago in my Herpetology class, we learned that some snakes still have their hind limbs, toes and all, but they are just vestigial. This is really interesting though, if the researchers in this article could make the limbs fully functional!

    Cynthia Bui (1)

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    1. Actually, the limbs that the researchers were able to induce were not really functional. They just noticed a significant increase in the limb bud outgrowth in these python embryos.There would certainly need to be other genes involved in creating a fully functional limb. However, it still stands that significant recovery of limb growth could be achieved by changing only one gene, illustrating the importance of toolkit genes.

      Sean McDougall

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  2. The loss of their limbs is very interesting. Snakes have developed very efficiently without the use of their limbs. Was there any particular reason why there was a loss of function in these genes?

    Kimberly Ty (3)

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    1. There seem to be two leading hypotheses for how snakes evolved limblessness. One is that they descended from borrowing lizards. Another is that they descend from marine reptiles that lived in the cretacous period. In both cases, limb loss was part of a streamlining of the body plan that was favored by selection, for either burrowing or swimming. I am not sure about the evolutionary origin of the specific mutations, only that they must have accumlated in certain lineages and been selected for. If you want to read more about the evolutionary origins of snakes, I have attached an article that goes through it.



      Sean McDougall

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    2. Sorry, forgot the attachment:

      http://www.sciencedirect.com.silk.library.umass.edu/science/article/pii/S0169534700019996

      Sean McDougall

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  3. Has there ever been any reports of snakes with legs that we are aware of? Since they have all the machinery there it seems not far from the scope of possibility.
    Tonya Sulham (3)

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  4. This is really interesting considering snakes lost their legs due to large changes in developmentally important genes, yet they are such a successful and widespread species of animal. I wonder if snakes lost their eyelids and external ears in the same way they lost their legs.


    Lindsey Dugas (1)

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  5. Did you find any information regarding whether snakes' ancestors lost these important genes due to a series of mutations and environmental changes. Wouldn't both would be necessary for this intense of a genetic change?

    -Ashley Sterpka (1)

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  6. FGFs seem to have many different functions, all having to do with inducing cell proliferation or growth (and not just in embryos). I'm sure you would be interested in how they can stimulate axon growth, based on the topics of your past posts.

    http://www.ncbi.nlm.nih.gov/pubmed/14664816

    Joseph Starrett(3)

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  7. Ok so the reason snakes lost there legs is because God said that they will slither among this earth and be afraid of man and women will be afraid of them.

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  8. Could inducing shh in forelimbs allow for leg development?

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