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A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins
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A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins
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Journal Article
A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins
2018
Overview
Despite their evolutionary, developmental and functional importance, the origin of vertebrate paired appendages remains uncertain. In mice, a single enhancer termed ZRS is solely responsible for
Shh
expression in limbs. Here, zebrafish and mouse transgenic assays trace the functional equivalence of ZRS across the gnathostome phylogeny. CRISPR/Cas9-mediated deletion of the medaka (
Oryzias latipes
) ZRS and enhancer assays identify the existence of ZRS shadow enhancers in both teleost and human genomes. Deletion of both ZRS and shadow ZRS abolishes
shh
expression and completely truncates pectoral fin formation. Strikingly, deletion of ZRS results in an almost complete ablation of the dorsal fin. This finding indicates that a ZRS-
Shh
regulatory module is shared by paired and median fins and that paired fins likely emerged by the co-option of developmental programs established in the median fins of stem gnathostomes.
Shh
function was later reinforced in pectoral fin development with the recruitment of shadow enhancers, conferring additional robustness.
The authors study the cis-regulatory evolution of the
Shh
locus in vertebrates. Using genomic editing and chromatin profiling, they conclude that paired fins emerged through the co-option of developmental programs for the median fins of gnathostomes.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Ablation
/ Animal Fins - growth & development
/ Animal Genetics and Genomics
/ Animals
/ Animals, Genetically Modified
/ Biomedical and Life Sciences
/ CRISPR
/ Extremities - growth & development
/ Fins
/ Genomes
/ Genomics
/ Hedgehog Proteins - genetics
/ Humans
/ Letter
/ Mice
/ Modules
/ Mutation
/ Oryzias - growth & development
/ Shadows
