Ancient origins of the vertebrate Hoxd appendage developmental system


Meeting Abstract

123.2  Tuesday, Jan. 7 13:45  Ancient origins of the vertebrate Hoxd appendage developmental system GEHRKE, A.R.*; SCHNEIDER, I.; NAKAMURA, T.; CHANDRAN, M.; BRAASCH, I.; POSTLETHWAIT, J.; SHUBIN, N.; The University of Chicago; The University of Chicago; The University of Chicago; The University of Chicago; The University of Oregon; The University of Oregon; The University of Chicago agehrke@uchicago.edu

Mammalian limbs are built by two sequential periods of Hox gene activation, commonly referred to as “early” and “late” phases that pattern proximal and distal segments, respectively. The regulatory systems responsible for the dual nature of Hoxd gene expression in limbs have been extensively studied in mouse, where early and late phase enhancers lie on opposite side of the HoxD cluster. Fish exhibit a similar pattern of Hoxd gene activation during fin development, but the extent to which these patterns are homologous with limbs remains controversial. We sought to identify the enhancers that control potential early and late phase Hoxd expression in a variety of fish species, including zebrafish, gar, and skate. Using multiple sequence alignments with key taxa, we identified the ortholog of an early phase enhancer in the gar genome, which was subsequently cloned and injected in zebrafish in a reporter assay. This enhancer drove strong GFP expression in the fins beginning at 31 hours post fertilization, reminiscent of an “early” phase activation. Additionally, we identified the orthologs of a number of potential “late” phase enhancers in gar, zebrafish, and skate. We found that these enhancers activate expression in the distal fin of zebrafish in transgenic assays, much like their mammalian counterparts. Altogether, these data suggest an ancient origin of the vertebrate Hoxd appendage developmental system, and that changes in fin morphology may have resulted from modifications to this network rather than the evolution of novel expression domains.

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