title: Regulatory evolution of Tbx5 and the origin of paired appendages.
abstract: The diversification of paired appendages has been a major factor in the evolutionary radiation of vertebrates. Despite its importance, an understanding of the origin of paired appendages has remained elusive. To address this problem, we focused on T-box transcription factor 5 (Tbx5), a gene indispensable for pectoral appendage initiation and development. Comparison of gene expression in jawless and jawed vertebrates reveals that the Tbx5 expression in jawed vertebrates is derived in having an expression domain that extends caudal to the heart and gills. Chromatin profiling, phylogenetic footprinting, and functional assays enabled the identification of a Tbx5 fin enhancer associated with this apomorphic pattern of expression. Comparative functional analysis of reporter constructs reveals that this enhancer activity is evolutionarily conserved among jawed vertebrates and is able to rescue the finless phenotype of tbx5a mutant zebrafish. Taking paleontological evidence of early vertebrates into account, our results suggest that the gain of apomorphic patterns of Tbx5 expression and regulation likely contributed to the morphological transition from a finless to finned condition at the base of the vertebrate lineage.
authors: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637;
authors: Noritaka
authors: N
authors: Adachi
authors: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637;
authors: Molly
authors: M
authors: Robinson
authors: Laboratory Schools, University of Chicago, Chicago, IL 60637.
authors: Aden
authors: A
authors: Goolsbee
authors: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637; nshubin@uchicago.edu.
authors: Neil H
authors: NH
authors: Shubin
mesh_terms: D058500:Animal Fins / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D005075:Biological Evolution; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D018983:DNA Footprinting; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007568:Jaw / Q000033:anatomy & histology; D007798:Lampreys / Q000033:anatomy & histology / Q000145:classification / Q000235:genetics / Q000254:growth & development; D010802:Phylogeny; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology / Q000145:classification / Q000235:genetics* / Q000254:growth & development
chemical_list: D002843:Chromatin; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D049452:Green Fluorescent Proteins
keywords: Tbx5 enhancer; development; evolution; paired fins