Letters to Nature

Nature 399, 474-479 (3 June 1999) | doi:10.1038/20944; Received 27 January 1999; Accepted 24 March 1999

Developmental basis of limblessness and axial patterning in snakes

Martin J .Cohn1,2 & Cheryll Tickle2,3

  1. Division of Zoology, School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK
  2. Department of Anatomy and Physiology, Wellcome Trust Building, University of Dundee, MSI/WTB Complex, Dow Street, Dundee DD1 5EH, UK
  3. Department of Anatomy and Developmental Biology, University College London, Medawar Building, Gower Street, London WC1E 6BT, UK

Correspondence to: Martin J .Cohn1,2 Correspondence and requests for materials should be addressed to M.J.C. (e-mail: Email: M.J.Cohn@reading.ac.uk.)

The evolution of snakes involved major changes in vertebrate body plan organization, but the developmental basis of those changes is unknown. The python axial skeleton consists of hundreds of similar vertebrae, forelimbs are absent and hindlimbs are severely reduced. Combined limb loss and trunk elongation is found in many vertebrate taxa1, suggesting that these changes may be linked by a common developmental mechanism. Here we show that Hox gene expression domains are expanded along the body axis in python embryos, and that this can account for both the absence of forelimbs and the expansion of thoracic identity in the axial skeleton. Hindlimb buds are initiated, but apical-ridge and polarizing-region signalling pathways that are normally required for limb development are not activated. Leg bud outgrowth and signalling by Sonic hedgehog in pythons can be rescued by application of fibroblast growth factor or by recombination with chick apical ridge. The failure to activate these signalling pathways during normal python development may also stem from changes in Hox gene expression that occurred early in snake evolution.