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A Hox regulatory network of hindbrain segmentation is conserved to the base of vertebrates

Parker, Hugo J. and Bronner, Marianne E. and Krumlauf, Robb (2014) A Hox regulatory network of hindbrain segmentation is conserved to the base of vertebrates. Nature, 514 (7523). pp. 490-493. ISSN 0028-0836. PMCID PMC4209185. doi:10.1038/nature13723.

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A defining feature governing head patterning of jawed vertebrates is a highly conserved gene regulatory network that integrates hindbrain segmentation with segmentally restricted domains of Hox gene expression. Although non-vertebrate chordates display nested domains of axial Hox expression, they lack hindbrain segmentation. The sea lamprey, a jawless fish, can provide unique insights into vertebrate origins owing to its phylogenetic position at the base of the vertebrate tree. It has been suggested that lamprey may represent an intermediate state where nested Hox expression has not been coupled to the process of hindbrain segmentation. However, little is known about the regulatory network underlying Hox expression in lamprey or its relationship to hindbrain segmentation. Here, using a novel tool that allows cross-species comparisons of regulatory elements between jawed and jawless vertebrates, we report deep conservation of both upstream regulators and segmental activity of enhancer elements across these distant species. Regulatory regions from diverse gnathostomes drive segmental reporter expression in the lamprey hindbrain and require the same transcriptional inputs (for example, Kreisler (also known as Mafba), Krox20 (also known as Egr2a)) in both lamprey and zebrafish. We find that lamprey hox genes display dynamic segmentally restricted domains of expression; we also isolated a conserved exonic hox2 enhancer from lamprey that drives segmental expression in rhombomeres 2 and 4. Our results show that coupling of Hox gene expression to segmentation of the hindbrain is an ancient trait with origin at the base of vertebrates that probably led to the formation of rhombomeric compartments with an underlying Hox code.

Item Type:Article
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URLURL TypeDescription ReadCube access CentralArticle
Parker, Hugo J.0000-0001-7646-2007
Bronner, Marianne E.0000-0003-4274-1862
Krumlauf, Robb0000-0001-9102-7927
Additional Information:© 2014 Macmillan Publishers Limited. Received 15 May; accepted 31 July 2014. Published online 14 September 2014. We thank S. Green for sharing expertise, methods and managing the lamprey facility; T. Sauka-Spengler for in situ hybridization advice; M. Simoes-Costa and B. Uy for help with reporter constructs; J. McEllin, C. Nolte, C. Scott and L. Wiedemann for discussions and assistance with lamprey hox genes; M. Distel and R. Koster for the r3/r5-mCherry zebrafish line; M. Miller for graphic design; A. Ikmi for manuscript comments and the Stowers Institute aquatics facility for zebrafish care. H.J.P. and R.K. were supported by the Stowers Institute (RK grant #2013-1001). M.E.B. was supported by grants R01NS086907 and R01DE017911. Author Contributions H.J.P., R.K. and M.E.B. conceived this research program. H.J.P. conducted the experiments. H.J.P., R.K. and M.E.B. jointly analysed the data, discussed the ideas and interpretations and wrote the manuscript. Author Information The sequences for the lamprey hox1wand kreisler transcripts have been deposited in GenBank under accession numbers KM087087 (hox1w) and KM087088 (kreisler). All original source data have been deposited in the Stowers Institute Original Data Repository and are available online at websimr/. Reprints and permissions information is available at reprints. The authors declare no competing financial interests. Readers are welcome to comment on the online version of the paper. Correspondence and requests for materials should be addressed to R.K. (
Funding AgencyGrant Number
Stowers InstituteRK 2013-1001
Issue or Number:7523
PubMed Central ID:PMC4209185
Record Number:CaltechAUTHORS:20140909-171653236
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:49513
Deposited By: Joy Painter
Deposited On:14 Sep 2014 17:11
Last Modified:10 Nov 2021 18:45

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