{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:46:14Z","timestamp":1773297974450,"version":"3.50.1"},"reference-count":25,"publisher":"Proceedings of the National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,6,25]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1073\/pnas.1300592110","type":"journal-article","created":{"date-parts":[[2013,5,15]],"date-time":"2013-05-15T00:11:55Z","timestamp":1368576715000},"page":"10682-10686","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":88,"title":["Role of a polymorphism in a Hox\/Pax-responsive enhancer in the evolution of the vertebrate spine"],"prefix":"10.1073","volume":"110","author":[{"given":"Isabel","family":"Guerreiro","sequence":"first","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal;"},{"name":"Department of Genetics and Evolution, University of Geneva, Sciences III, 1211 Geneva 4, Switzerland;"}]},{"given":"Andreia","family":"Nunes","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal;"}]},{"given":"Joost M.","family":"Woltering","sequence":"additional","affiliation":[{"name":"Department of Genetics and Evolution, University of Geneva, Sciences III, 1211 Geneva 4, Switzerland;"}]},{"given":"Ana","family":"Casaca","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal;"}]},{"given":"Ana","family":"N\u00f3voa","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal;"}]},{"given":"T\u00e2nia","family":"Vinagre","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal;"}]},{"given":"Margaret E.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Southeast Ecological Science Center, US Geological Survey, Gainesville, FL 32653;"}]},{"given":"Denis","family":"Duboule","sequence":"additional","affiliation":[{"name":"Department of Genetics and Evolution, University of Geneva, Sciences III, 1211 Geneva 4, Switzerland;"},{"name":"School of Life Sciences, Ecole Polytechnique Federale, 1015 Lausanne, Switzerland; and"}]},{"given":"Mois\u00e9s","family":"Mallo","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal;"},{"name":"Department of Histology and Embryology, Faculty of Medicine, University of Lisbon, 1749-016 Lisbon, Portugal"}]}],"member":"341","published-online":{"date-parts":[[2013,5,14]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0092-8674(94)90290-9","article-title":"Hox genes in vertebrate development","volume":"78","author":"Krumlauf R","year":"1994","unstructured":"R Krumlauf, Hox genes in vertebrate development. 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Dev Dyn 236, 2454\u20132463 (2007).","journal-title":"Dev Dyn"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1126\/science.1085672","article-title":"Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton","volume":"301","author":"Wellik DM","year":"2003","unstructured":"DM Wellik, MR Capecchi, Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science 301, 363\u2013367 (2003).","journal-title":"Science"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1101\/gad.338705","article-title":"Hox genes specify vertebral types in the presomitic mesoderm","volume":"19","author":"Carapu\u00e7o M","year":"2005","unstructured":"M Carapu\u00e7o, A N\u00f3voa, N Bobola, M Mallo, Hox genes specify vertebral types in the presomitic mesoderm. Genes Dev 19, 2116\u20132121 (2005).","journal-title":"Genes Dev"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature08789","article-title":"Changes in Hox genes\u2019 structure and function during the evolution of the squamate body plan","volume":"464","author":"Di-Po\u00ef N","year":"2010","unstructured":"N Di-Po\u00ef, et al., Changes in Hox genes\u2019 structure and function during the evolution of the squamate body plan. Nature 464, 99\u2013103 (2010).","journal-title":"Nature"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ydbio.2009.04.031","article-title":"Axial patterning in snakes and caecilians: Evidence for an alternative interpretation of the Hox code","volume":"332","author":"Woltering JM","year":"2009","unstructured":"JM Woltering, et al., Axial patterning in snakes and caecilians: Evidence for an alternative interpretation of the Hox code. 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