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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.

SUBMITTER: Guerreiro I 

PROVIDER: S-EPMC3696775 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Role of a polymorphism in a Hox/Pax-responsive enhancer in the evolution of the vertebrate spine.

Guerreiro Isabel I   Nunes Andreia A   Woltering Joost M JM   Casaca Ana A   Nóvoa Ana A   Vinagre Tânia T   Hunter Margaret E ME   Duboule Denis D   Mallo Moisés M  

Proceedings of the National Academy of Sciences of the United States of America 20130514 26


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 ra  ...[more]

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