ArticleProceedings of the National Academy of Sciences of the United States of America2013
Role of a polymorphism in a Hox/Pax-responsive enhancer in the evolution of the vertebrate spine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 92 citations in OpenAlex.
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- Abnormal level of CUL4B-mediated histone H2A ubiquitination causes disruptive HOX gene expression.Epigenetics & chromatin · 2019Article
- Hoxa13 regulates expression of common Hox target genes involved in cartilage development to coordinate the expansion of the autopodal anlage.Development, growth & differentiation · 2019Article
- A QTL for Number of Teats Shows Breed Specific Effects on Number of Vertebrae in Pigs: Bridging the Gap Between Molecular and Quantitative Genetics.Frontiers in genetics · 2019Article
- Identification of a limb enhancer that is removed by pathogenic deletions downstream of the SHOX gene.Scientific reports · 2018Article
- Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution.Molecular systems biology · 2018Article
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9 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.