1. Evolution: Enhanced Footing for Snake Limb Development
Maria M. Kaltcheva, Mark Lewandoski 
Current Biology 
Volume 26, Issue 23, Pages R1237-R1240 (December 2016)
DOI: /j.cub
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2. Figure 1 Functionality of the Shh enhancer in mice and snakes.
Dashed line delineates between analysis in mouse (top) and snake (bottom). (A) The ZRS is a cis-acting, long-distance enhancer (left column) necessary for proper posterior Shh limb bud expression (middle column) and normal limb development (right column). (B) In the mouse, inactivation of either the coding region or the ZRS results in no Shh expression and reduced limb development. (C) The cobra ZRS provides no Shh expression and results in a Shh null phenoytpe. (D) The python ZRS provides minimal Shh expression and slightly improved limb development. (E) ‘Resurrecting’ the python ZRS by inserting a 17 bp mouse sequence rescues normal Shh expression and limb development. (F) During normal python development, the ZRS can transiently activate Shh expression, resulting in truncated vestigial hindlimbs. (G) The cobra, an evolutionarily advanced snake, does not initiate limb bud outgrowth during development and lacks adult limb skeletal elements. (H) Would replacing the python ZRS with the sequence from a mouse restore Shh expression in the limb bud, allowing limb development to proceed? Blue denotes mouse DNA. Orange denotes snake DNA. Light orange denotes evolutionary degeneration of ZRS sequence in snakes.
Current Biology  , R1237-R1240DOI: ( /j.cub )
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