ArticleCurrent biology : CB2016
Loss and Re-emergence of Legs in Snakes by Modular Evolution of Sonic hedgehog and HOXD Enhancers.
Article in Current biology : CB, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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62 citing papers in PubMed, 116 citations in OpenAlex.
- Loss, persistence and reversal of phenotypic traits.Biological reviews of the Cambridge Philosophical Society · 2026Review
- The genomic origins and evolutionary path to a key innovation in the world's most venomous snakes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The genomic origins and evolutionary path to a key innovation in the world's most venomous snakes.bioRxiv : the preprint server for biology · 2026Article
- Distinct mechanisms decommission redundant enhancers to facilitate phenotypic evolution.Science advances · 2026Article
- Systematic enhancer mapping and functional analysis in zebrafish with optimized CRISPR interference.Nucleic acids research · 2025Article
- Evolution of cetacean-specific conserved non-coding elements suggests their role in the limb changes during secondary aquatic adaptation.BMC biology · 2025Article
- Correlated evolution of multiple traits gives butterflies a false head.Proceedings. Biological sciences · 2025Article
- Epigenomic signatures of cis-regulatory elements in the developing mouse and pig forelimb.Scientific data · 2025Article
- Functional evidence supports the potential role of Tbx4-HLEA in the hindlimb degeneration of cetaceans.EvoDevo · 2025Article
- Convergent Evolution Has Led to the Loss of Claw Proteins in Snakes and Worm Lizards.Genome biology and evolution · 2025Article
- The 3' region of the ZPA regulatory sequence (ZRS) is required for activity and contains a critical E-box.Frontiers in cell and developmental biology · 2025Article
- Embryonic Development and Cranial Ossification Sequence in TwoLife (Basel, Switzerland) · 2024Article
- A new cell culture resource for investigations of reptilian gene function.Development (Cambridge, England) · 2024Article
- Convergent Degenerated Regulatory Elements Associated with Limb Loss in Limbless Amphibians and Reptiles.Molecular biology and evolution · 2024Article
- Ancient developmental genes underlie evolutionary novelties in walking fish.Current biology : CB · 2024Article
- Tgfbr1 controls developmental plasticity between the hindlimb and external genitalia by remodeling their regulatory landscape.Nature communications · 2024Article
- Identification and characterization of Hand2 upstream genomic enhancers active in developing stomach and limbs.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- Review
- The genetic basis of novel trait gain in walking fish.bioRxiv : the preprint server for biology · 2023Article
- Developmental regulation of conserved non-coding element evolution provides insights into limb loss in squamates.Science China. Life sciences · 2023Article
2 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
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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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.