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Conservation and elaboration of Hox gene regulation during evolution of the vertebrate head

Abstract

The comparison of Hox genes between vertebrates and their closest invertebrate relatives (amphioxus and ascidia) highlights two derived features of Hox genes in vertebrates: duplication of the Hox gene cluster1,2, and an elaboration of Hox expression patterns and roles compared with non-vertebrate chordates3,4,5,6,7,8. We have investigated how new expression domains and their associated developmental functions evolved, by testing the cis-regulatory activity of genomic DNA fragments from the cephalochordate amphioxus Hox cluster in transgenic mouse and chick embryos. Here we present evidence for the conservation of cis-regulatory mechanisms controlling gene expression in the neural tube for half a billion years of evolution, including a dependence on retinoic acid signalling. We also identify amphioxus Hox gene regulatory elements that drive spatially localized expression in vertebrate neural crest cells, in derivatives of neurogenic placodes and in branchial arches, despite the fact that cephalochordates lack both neural crest and neurogenic placodes. This implies an elaboration of cis-regulatory elements in the Hox gene cluster of vertebrate ancestors during the evolution of craniofacial patterning.

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Figure 1: Transgenic analysis of the 3′ end of the amphioxus Hox complex.
Figure 2: Neural expression mediated by amphioxus Hox regulatory elements in mouse and chick embryos.
Figure 3: Element 1A directs expression in neural crest cells and placodes of chick embryos.
Figure 4: Expression in neurogenic placodal and mesodermal derivatives mediated by amphioxus Hox elements.

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Acknowledgements

We thank S. Bel-Vialar for electroporating some of the constructs; A. Hewett, P. Mealyer and R. Murphy for animal husbandry; N. Williams, J. Millard and J. Hornby for assistance with transgenic analysis; and J. Garcia-Fernàndez, A. Nieto and members of the Krumlauf laboratory for comments and suggestions. M.M. was supported by HFSP and EU Marie Curie Fellowships; H.W. by a HFSP Fellowship; N.I. by Uehara and HFSP Fellowships; and P.T. by EMBO and HFSP Fellowships. This work was funded in part by an EEC Biotechnology Network grant and core MRC Programme support to R.K., the Nissan Science Foundation and a Grant-in-Aid from the Ministry of Education, Science and Culture of Japan to H.W., BBSRC support to P.W.H.H., and facilitated by a British Council and JSPS Collaborative Research Project grant to P.W.H.H. and H.W.

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Correspondence to Peter W. H. Holland.

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Manzanares, M., Wada, H., Itasaki, N. et al. Conservation and elaboration of Hox gene regulation during evolution of the vertebrate head. Nature 408, 854–857 (2000). https://doi.org/10.1038/35048570

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