Unwinding Limb Development Diego Villar, Duncan T. Odom  Cell  Volume 167, Issue 3, Pages 598-600 (October 2016) DOI: 10.1016/j.cell.2016.10.007 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 The Phenotypic Effect of a Snake-Specific Deletion in a Limb Enhancer (A–C) Most snakes have evolved complete limb loss (center). Similarly in mammals, whales and dolphins have lost their hind limbs, and conversely, bats have massively remodelled segments of their forelimbs. The ZRS is a well-characterized long-range enhancer directing limb-specific expression of Sonic hedgehog. Kvon et al. (2016) employ a combination of comparative genomics and genetic engineering to introduce snake-specific deletions in this enhancer element into the orthologous mouse genome, resulting in truncated limb development in vivo. The sequence alignment of human, coelacanth, python, and cobra sequences corresponds to a 42 bp region of the ZRS containing a serpent-specific deletion. Numbers below each species silhouette indicate percentage nucleotide identity over the core ZRS (∼0.8 kb), using the mouse enhancer as reference. ZRS, Zone of Polarizing Activity Regulatory Sequence; Shh, Sonic hedgehog. (A) Image from iStock.com/JackF. (B) Image from iStock.com/draskovic. (C) Image from iStock.com/poetrygirl128. Cell 2016 167, 598-600DOI: (10.1016/j.cell.2016.10.007) Copyright © 2016 Elsevier Inc. Terms and Conditions