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标题：Deep conservation of wrist and digit enhancers in fish
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作者：Andrew R. Gehrke ; Igor Schneider ; Elisa de la Calle-Mustienes 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：3
页码：803-808
DOI：10.1073/pnas.1420208112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe fossil record shows that the wrist and digits have an aquatic origin, becoming recognizable in a group of (mostly extinct) fish that contained robust fins. Do the fins of living fishes have the equivalent of these structures? Because comparisons of fin and limb morphology have been inconclusive, we sought to investigate this question using developmental and molecular data. By utilizing a nonmodel fish (the spotted gar), we find that the regulatory networks that control "wrist and digit"-building genes (Hox) are deeply conserved between fish and tetrapods. The genomic architecture described here defines Hox gene activity in fins and limbs as equivalent, in turn suggesting equivalence between the distal bones of fish fins and the wrist and/or digits of tetrapods. 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.
关键词：evolution ; development ; autopod ; gene regulation ; Hox