title: Role of a polymorphism in a Hox/Pax-responsive enhancer in the evolution of the vertebrate spine.
abstract: Patterning of the vertebrate skeleton requires the coordinated activity of Hox genes. In particular, Hox10 proteins are essential to set the transition from thoracic to lumbar vertebrae because of their rib-repressing activity. In snakes, however, the thoracic region extends well into Hox10-expressing areas of the embryo, suggesting that these proteins are unable to block rib formation. Here, we show that this is not a result of the loss of rib-repressing properties by the snake proteins, but rather to a single base pair change in a Hox/Paired box (Pax)-responsive enhancer, which prevents the binding of Hox proteins. This polymorphism is also found in Paenungulata, such as elephants and manatees, which have extended rib cages. In vivo, this modified enhancer failed to respond to Hox10 activity, supporting its role in the extension of rib cages. In contrast, the enhancer could still interact with Hoxb6 and Pax3 to promote rib formation. These results suggest that a polymorphism in the Hox/Pax-responsive enhancer may have played a role in the evolution of the vertebrate spine by differently modulating its response to rib-suppressing and rib-promoting Hox proteins.
authors.affiliation: Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Guerreiro
authors.forename: Andreia
authors.initials: A
authors.lastname: Nunes
authors.forename: Joost M
authors.initials: JM
authors.lastname: Woltering
authors.forename: Ana
authors.initials: A
authors.lastname: Casaca
authors.forename: Ana
authors.initials: A
authors.lastname: Nóvoa
authors.forename: Tânia
authors.initials: T
authors.lastname: Vinagre
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Hunter
authors.forename: Denis
authors.initials: D
authors.lastname: Duboule
authors.forename: Moisés
authors.initials: M
authors.lastname: Mallo
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics; D017812:Colubridae / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D005801:Genes, Homeobox; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012689:Sequence Homology, Nucleic Acid; D013131:Spine / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D051787:Myogenic Regulatory Factor 5; D051761:Paired Box Transcription Factors; C092119:Hoxa10 protein, mouse
keywords: axial skeleton; gene regulation; vertebrate patterning