Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 3, Pages 803-808Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1420208112
Keywords
evolution; development; autopod; gene regulation; Hox
Categories
Funding
- Brinson Foundation
- National Science Foundation Doctoral Dissertation Improvement [1311436]
- Brazilian National Council for Scientific and Technological Development [402754/2012-3, 477658/2012-1]
- National Institutes of Health [R01RR020833 (R01OD011116)]
- Volkswagen Foundation, Germany
- Alexander von Humboldt-Foundation
- Spanish and Andalusian Governments [BFU2010-14839, BFU2013-41322-P]
- Proyecto de Excelencia [BIO-396]
- Division Of Environmental Biology
- Direct For Biological Sciences [1311436] Funding Source: National Science Foundation
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There is no obvious morphological counterpart of the autopod (wrist/ankle and digits) in living fishes. Comparative molecular data may provide insight into understanding both the homology of elements and the evolutionary developmental mechanisms behind the fin to limb transition. In mouse limbs the autopod is built by a late phase of Hoxd and Hoxa gene expression, orchestrated by a set of enhancers located at the 5' end of each cluster. Despite a detailed mechanistic understanding of mouse limb development, interpretation of Hox expression patterns and their regulation in fish has spawned multiple hypotheses as to the origin and function of autopod enhancers throughout evolution. Using phylogenetic footprinting, epigenetic profiling, and transgenic reporters, we have identified and functionally characterized hoxD and hoxA enhancers in the genomes of zebrafish and the spotted gar, Lepisosteus oculatus, a fish lacking the whole genome duplication of teleosts. Gar and zebrafish autopod enhancers drive expression in the distal portion of developing zebrafish pectoral fins, and respond to the same functional cues as their murine orthologs. Moreover, gar enhancers drive reporter gene expression in both the wrist and digits of mouse embryos in patterns that are nearly indistinguishable from their murine counterparts. These functional genomic data support the hypothesis that the distal radials of bony fish are homologous to the wrist and/or digits of tetrapods.
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