Loss and Re-emergence of Legs in Snakes by Modular Evolution of Sonic hedgehog and HOXD Enhancers - PubMed

Affiliations

• PMID: 27773569
• DOI: 10.1016/j.cub.2016.09.020

Free article

Loss and Re-emergence of Legs in Snakes by Modular Evolution of Sonic hedgehog and HOXD Enhancers

Francisca Leal et al. Curr Biol. 2016.

Free article

Abstract

Limb reduction and loss are hallmarks of snake evolution. Although advanced snakes are completely limbless, basal and intermediate snakes retain pelvic girdles and small rudiments of the femur. Moreover, legs may have re-emerged in extinct snake lineages [1-5], suggesting that the mechanisms of limb development were not completely lost in snakes. Here we report that hindlimb development arrests in python embryos as a result of mutations that abolish essential transcription factor binding sites in the limb-specific enhancer of Sonic hedgehog (SHH). Consequently, SHH transcription is weak and transient in python hindlimb buds, leading to early termination of a genetic circuit that drives limb outgrowth. Our results suggest that degenerate evolution of the SHH limb enhancer played a role in reduction of hindlimbs during snake evolution. By contrast, HOXD digit enhancers are conserved in pythons, and HOXD gene expression in the hindlimb buds progresses to the distal phase, forming an autopodial (digit) domain. Python hindlimb buds then develop transitory pre-chondrogenic condensations of the tibia, fibula, and footplate, raising the possibility that re-emergence of hindlimbs during snake evolution did not require de novo re-evolution of lost structures but instead could have resulted from persistence of embryonic legs. VIDEO ABSTRACT.

Keywords: ZRS; anole; digits; embryo; evo-devo; genome; limb bud; limblessness; python; skeleton.

Comment in

• Evolution: Enhanced Footing for Snake Limb Development.

  Kaltcheva MM, Lewandoski M. Kaltcheva MM, et al. Curr Biol. 2016 Dec 5;26(23):R1237-R1240. doi: 10.1016/j.cub.2016.10.018. Curr Biol. 2016. PMID: 27923134

Similar articles

• Developmental, genetic, and genomic insights into the evolutionary loss of limbs in snakes.

  Leal F, Cohn MJ. Leal F, et al. Genesis. 2018 Jan;56(1). doi: 10.1002/dvg.23077. Epub 2017 Nov 2. Genesis. 2018. PMID: 29095557 Review.

• Developmental basis of limblessness and axial patterning in snakes.

  Cohn MJ, Tickle C. Cohn MJ, et al. Nature. 1999 Jun 3;399(6735):474-9. doi: 10.1038/20944. Nature. 1999. PMID: 10365960

• Progressive Loss of Function in a Limb Enhancer during Snake Evolution.

  Kvon EZ, Kamneva OK, Melo US, Barozzi I, Osterwalder M, Mannion BJ, Tissières V, Pickle CS, Plajzer-Frick I, Lee EA, Kato M, Garvin TH, Akiyama JA, Afzal V, Lopez-Rios J, Rubin EM, Dickel DE, Pennacchio LA, Visel A. Kvon EZ, et al. Cell. 2016 Oct 20;167(3):633-642.e11. doi: 10.1016/j.cell.2016.09.028. Cell. 2016. PMID: 27768887 Free PMC article.

• Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function.

  Chiang C, Litingtung Y, Harris MP, Simandl BK, Li Y, Beachy PA, Fallon JF. Chiang C, et al. Dev Biol. 2001 Aug 15;236(2):421-35. doi: 10.1006/dbio.2001.0346. Dev Biol. 2001. PMID: 11476582

• How the embryo makes a limb: determination, polarity and identity.

  Tickle C. Tickle C. J Anat. 2015 Oct;227(4):418-30. doi: 10.1111/joa.12361. Epub 2015 Aug 7. J Anat. 2015. PMID: 26249743 Free PMC article. Review.

Cited by

• 3D genomics and its applications in precision medicine.

  Chen M, Liu X, Liu Q, Shi D, Li H. Chen M, et al. Cell Mol Biol Lett. 2023 Mar 6;28(1):19. doi: 10.1186/s11658-023-00428-x. Cell Mol Biol Lett. 2023. PMID: 36879202 Free PMC article.

• The ecological origins of snakes as revealed by skull evolution.

  Da Silva FO, Fabre AC, Savriama Y, Ollonen J, Mahlow K, Herrel A, Müller J, Di-Poï N. Da Silva FO, et al. Nat Commun. 2018 Jan 25;9(1):376. doi: 10.1038/s41467-017-02788-3. Nat Commun. 2018. PMID: 29371624 Free PMC article.

• John Saunders' ZPA, Sonic hedgehog and digit identity - How does it really all work?

  Zhu J, Mackem S. Zhu J, et al. Dev Biol. 2017 Sep 15;429(2):391-400. doi: 10.1016/j.ydbio.2017.02.001. Epub 2017 Feb 2. Dev Biol. 2017. PMID: 28161524 Free PMC article. Review.

• Spatial regulation by multiple Gremlin1 enhancers provides digit development with cis-regulatory robustness and evolutionary plasticity.

  Malkmus J, Ramos Martins L, Jhanwar S, Kircher B, Palacio V, Sheth R, Leal F, Duchesne A, Lopez-Rios J, Peterson KA, Reinhardt R, Onimaru K, Cohn MJ, Zuniga A, Zeller R. Malkmus J, et al. Nat Commun. 2021 Sep 21;12(1):5557. doi: 10.1038/s41467-021-25810-1. Nat Commun. 2021. PMID: 34548488 Free PMC article.

• Sonic Hedgehog Signaling in Limb Development.

  Tickle C, Towers M. Tickle C, et al. Front Cell Dev Biol. 2017 Feb 28;5:14. doi: 10.3389/fcell.2017.00014. eCollection 2017. Front Cell Dev Biol. 2017. PMID: 28293554 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • H1 Connect
  • scite Smart Citations

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)