title: Shared Enhancer Activity in the Limbs and Phallus and Functional Divergence of a Limb-Genital cis-Regulatory Element in Snakes.
abstract: The amniote phallus and limbs differ dramatically in their morphologies but share patterns of signaling and gene expression in early development. Thus far, the extent to which genital and limb transcriptional networks also share cis-regulatory elements has remained unexplored. We show that many limb enhancers are retained in snake genomes, suggesting that these elements may function in non-limb tissues. Consistent with this, our analysis of cis-regulatory activity in mice and Anolis lizards reveals that patterns of enhancer activity in embryonic limbs and genitalia overlap heavily. In mice, deletion of HLEB, an enhancer of Tbx4, produces defects in hindlimbs and genitalia, establishing the importance of this limb-genital enhancer for development of these different appendages. Further analyses demonstrate that the HLEB of snakes has lost hindlimb enhancer function while retaining genital activity. Our findings identify roles for Tbx4 in genital development and highlight deep similarities in cis-regulatory activity between limbs and genitalia.
authors.affiliation: Department of Genetics, University of Georgia, Athens, GA 30602, USA.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Infante
authors.affiliation: Department of Genetics, University of Georgia, Athens, GA 30602, USA.
authors.forename: Alexandra G
authors.initials: AG
authors.lastname: Mihala
authors.affiliation: Department of Genetics, University of Georgia, Athens, GA 30602, USA.
authors.forename: Sungdae
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Genetics, University of Georgia, Athens, GA 30602, USA.
authors.forename: Jialiang S
authors.initials: JS
authors.lastname: Wang
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Kenji K
authors.initials: KK
authors.lastname: Johnson
authors.affiliation: Department of Genetics, University of Georgia, Athens, GA 30602, USA; Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Lauderdale
authors.affiliation: Department of Genetics, University of Georgia, Athens, GA 30602, USA. Electronic address: dmenke@uga.edu.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Menke
mesh_terms: D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D005835:Genitalia / Q000196:embryology* / Q000378:metabolism; D016678:Genome; D017403:In Situ Hybridization; D008116:Lizards; D051379:Mice; D018345:Mice, Knockout; D038081:Organogenesis / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012911:Snakes; D020825:T-Box Domain Proteins / Q000502:physiology*
chemical_list: D020825:T-Box Domain Proteins; C103177:Tbx4 protein, mouse