Ferrier Lab: Research


Research at the School of Biology

Key Research Areas:

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We aim to understand how the diversity of animal form develops and evolved. The focus of our research is the connection between the content and organisation of genomes to the evolution of development (evo-devo). The homeobox-containing genes of the Hox gene cluster have been a corner-stone of Evolutionary Developmental Biology, but much about cluster organisation and mode of operation remains unknown.

Fluorescent chromosome in situ hybridisation of ANTP-class genes in Platynereis dumerilii.

Reconstruction of the Urbilaterian Super-Hox cluster (adapted from Butts et al (2008) TiGs 24,259-62).

Research

Evolution of the organisation of the ANTP-class of homeobox genes.

The clustered organisation of many homeobox-containing genes can have functional implications, as with the Hox cluster, but can also reveal the evolutionary history of these important developmental control genes as well as the evolutionary dynamics of animal genomes. Patterns of gene origin, gene loss, linkage and clustering are being revealed by analysis of the genomes of representative taxa from across the animals.

Butts, T., Holland, P.W.H. and Ferrier, D.E.K. The Urbilaterian Super-Hox cluster. Trends in Genetics (2008) 24(6), 259-262.
Hui, J.H.L., Holland, P.W.H. and Ferrier, D.E.K. Do cnidarians have a ParaHox cluster? Analysis of synteny around a Nematostella homeobox gene cluster.
Evolution and Development (2008) 10, 725-730.
Tribolium Sequencing Consortium (Richards, S. et al.). The genome of the developmental model beetle and pest Tribolium castaneum. Nature (2008) 452, 949-955.

Polychaete development and genome evolution

Adult Pomatoceros lamarckii removed from habitation tube.

It is now clear that polychaetes can provide us with a model system that is much less derived from the ancestral bilaterian condition than are more traditional model systems within the protostomes, such as flies and nematodes. The keelworm, Pomatoceros, is a tube-dwelling, intertidal polychaete that is widespread around the British Isles and is readily accessible for molecular and embryological work.

We are studying the embryogenesis of this annelid for comparative purposes and are beginning to investigate the organisation and expression of its developmental genes. The nereid, Platynereis dumerilii, provides a second polychaete for comparison, to enable a more robust reconstruction of polychaete evo-devo and genomics for comparisons to other phyla.

Torres, M.L., Antkowiak, M., Cizmarova, H., Ferrier, D.E.K., Dholakia, K. & Gunn-Moore, F.J. Integrated holographic system for all-optical manipulation of developing embryos. Biomedical Optics Express (2011), 2(6), 1564-1575.
Takahashi, T., McDougall, C., Troschianko, J., Chen, W-C., Nagarajan, A.J., Shimeld, S.M. and Ferrier, D.E.K. An EST screen from the annelid Pomatoceros lamarckii reveals patterns of gene loss and gain in animals. BMC Evolutionary Biology (2009) 9:240.
McDougall, C., Hui, J.H.L., Monteiro, A., Takahashi, T. and Ferrier, D.E.K. Annelids in evolutionary developmental biology and comparative genomics. Parasite (2008) 15, 321-328.
McDougall, C., Chen, W-C., Shimeld, S.M. and Ferrier, D.E.K. The development of the larval nervous system, musculature and ciliary bands of Pomatoceros lamarckii (Annelida): heterochrony in polychaetes. Frontiers in Zoology (2006) 3, 16.
Denes, A.S., Jékely, G., Steinmetz, P.R., Raible, F., Snyman, H., Klaus, S., Prud’homme, B., Ferrier, D.E.K., Balavoine, G. and Arendt, D. Mediolateral arrangement of neurogenic columns and of neuron types in the polychaete trunk central nervous system. Cell. (2007) 129, 277-288.
Raible, F., Tessmar-Raible, K., Osoegawa, K., Wincker, P., Jubin, C., Balavoine, G., Ferrier, D.E.K., Benes, V., de Jong, P., Weissenbach, J., Bork, P. and Arendt. D. Vertebrate-type intron-rich genes in the marine annelid Platynereis dumerilii. Science (2005) 310, 1325-1326.

Regeneration and biomineralization in lophotrochozoans.

The polychaete, Pomatoceros lamarckii, provides a useful new system in which to study both regeneration and biomineralization. Regeneration of the head appendages of Pomatoceros can be easily induced and occurs relatively rapidly over the course of a few days. Combined with the relatively conservative nature of polychaete gene sequence and content evolution this system should provide us with an informative new, accessible system in which to address comparative aspects of animal regeneration. In the Pomatoceros system this includes biomineralization, since the operculum appendage produces a protective calcified plate (in addition to its calcareous habitation tube).

Takahashi, T., McDougall, C., Troschianko, J., Chen, W-C., Nagarajan, A.J., Shimeld, S.M. and Ferrier, D.E.K. An EST screen from the annelid Pomatoceros lamarckii reveals patterns of gene loss and gain in animals. BMC Evolutionary Biology (2009) 9:240.
McDougall, C., Chen, W-C., Shimeld, S.M. and Ferrier, D.E.K. The development of the larval nervous system, musculature and ciliary bands of Pomatoceros lamarckii (Annelida): heterochrony in polychaetes. Frontiers in Zoology (2006) 3, 16.

Evolution of the homeobox gene content of chordates

Retention and loss of homeobox families in chordates (adapted from Holland et al (2008) Genome Research 18,1100-1111).

The recently sequenced genome of amphioxus (Branchiostoma floridae), a basal lineage of chordates, is proving to be immensely valuable for revealing characteristics of the organisation of the genomes of the chordate and vertebrate ancestors. Amphioxus has retained the full complement of homeobox gene families that are inferred to have been present in the chordate ancestor.

Other chordate lineages have lost some of these gene families. Amphioxus thus provides us with a system with which to understand how these important developmental control genes have been involved in the evolution of the animal lineage containing humans.

Butts, T., Holland, P.W.H. and Ferrier, D.E.K. Ancient homeobox gene loss and the evolution of chordate brain and pharynx development: deductions from amphioxus gene expression. Proceedings of the Royal Society B. (2010) 277, 3381-3389.
Holland, L.Z., et al. The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Research (2008) 18, 1100-1111.
Putnam, N.H. et al. The amphioxus genome and the evolution of the chordate karyotype. Nature (2008) 453, 1064-1071.
Takatori, N., Butts, T., Candiani, S., Pestarino, M., Ferrier, D.E.K., Saiga, H. and Holland, P.W.H. Comprehensive survey and classification of homeobox genes in the genome of amphioxus, Branchiostoma floridae. Development Genes and Evolution (2008) 218, 579-590.

Chordate muscle genes and genome duplications.

Amphioxus possesses clear segmented, myomeric musculature that is an important point of comparison to vertebrate muscles for understanding the origins and evolution of vertebrate somatic musculature. The whole genome duplications that occurred at the origins of vertebrates (the 2R hypothesis) and then again early in teleost evolution (the 3R hypothesis) had important impacts on the composition of all sorts of gene networks, including those controlling muscle development and function. Amphioxus provides an excellent outgroup comparison to the vertebrates, such as the conventional models in developmental biology (e.g. mouse, chick, zebrafish) as well as important sources of food (e.g. salmon, carp), which will enable the impacts of these large-scale duplication events on muscle gene networks to be deduced.

Holland, L.Z., et al. The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Research (2008) 18, 1100-1111.
Putnam, N.H. et al. The amphioxus genome and the evolution of the chordate karyotype. Nature (2008) 453, 1064-1071.

Evolution of bilaterian animal Hox cluster organisation

Adapted from Holland et al (2008) Genome Research 18,1100-1111.

The Hox gene cluster patterns the anterior-posterior axis of bilaterian animals. In animals such as mice the organisation of the genes within the cluster is intimately associated with how the genes are regulated and function during embryogenesis. In other lineages, such as flies, nematodes and urochordates there is no such constraint on cluster maintenance, and the Hox clusters in these animals have broken apart.

In order to understand the role that the Hox cluster has had in animal evolution it is imperative to discover the organisation of the cluster in a wide variety of lineages and the mechanisms regulating the genes in these diverse taxa. We are attempting to characterise the Hox clusters of several lineages of supposedly less-derived animals (amphioxus, polychaetes and priapulids) as a means to understanding the ancestral forms of the cluster across the bilaterians.

Holland, L.Z., et al. The amphioxus genome illuminates vertebrate origins and cephalochordate biology. Genome Research (2008) 18, 1100-1111.
Amemiya, C.T., Prohaska, S.J., Hill-Force, A., Cook, A., Wasserscheid, J., Ferrier, D.E.K., Pascual-Anaya, J., Garcia-Fernàndez, J., Dewar, K. and Stadler, P.F. The amphioxus Hox cluster: characterization, comparative genomics, and evolution. Journal of Experimental Zoology (Mol Dev Evol) (2008) 310B, 465-477.
Monteiro, A.S. and Ferrier, D.E.K. Hox genes are not always Colinear. International Journal of Biological Sciences (2006) 2, 95-103.
Ferrier, D.E.K. and Holland P.W.H. Ancient origin of the Hox gene cluster. Nature Reviews Genetics (2001) 2, 33-38.
Ferrier, D.E.K., Minguillón, C., Holland, P.W.H., and Garcia-Fernàndez, J. The amphioxus Hox cluster : deuterostome posterior flexibility and Hox14. Evolution and Development(2000) 2, 284-293.
Ferrier, D.E.K. and Akam, M. Organization of the Hox gene cluster in the grasshopper, Schistocerca gregaria. PNAS (1996) 93, 13024-13029.

Evolution of chordate ParaHox gene regulation

Expression of AmphiXlox (black) and AmphiCdx (red) in an amphioxus neurula (by Peter Osborne). See Osborne et al (2009) Dev Biol 327,252-262.

The ParaHox gene cluster is the evolutionary sister to the Hox gene cluster. It has so far only been characterised in chordate taxa, where it also seems to play a role in patterning aspects of the anterior-posterior axis of embryos like its Hox sister.

We are investigating how the ParaHox genes are regulated in the basal chordate lineages of amphioxus and sea squirts as a means to understand the fundamental mechanisms controlling these genes in chordates.

Osborne, P.W. and Ferrier, D.E.K. Chordate Hox and ParaHox gene clusters differ dramatically in their repetitive element content. Molecular Biology and Evolution (2010) 27(2), 217-220.
Osborne, P.W., Benoit, G., Laudet, V., Schubert , M. and Ferrier, D.E.K. Differential regulation of ParaHox genes by retinoic acid in the invertebrate chordate amphioxus (Branchiostoma floridae). Developmental Biology, 327, 252-262.
Ferrier, D.E.K., Dewar, K., Cook, A., Chang, J.L., Hill-Force, A., and Amemiya, C. The chordate ParaHox cluster. Current Biology (2005) 15, R820-R822.

Polychaete ParaHox genes

Expression of Pdu-Gsx in Platynereis stomodeum development (see Hui et al (2009) BMC Biology, in press).

To understand the role that the ParaHox genes may have played in animal evolution, and whether they have been as vital as the famous Hox genes, their organisation and expression must be understood in a much greater variety of taxa than have currently been investigated.

In particular flies and nematodes are of limited value in this endeavour since they have broken up the ParaHox cluster and lost some of the genes. Alternative protostome models are required, such as the polychaetes, which have retained all three ParaHox genes.

Hui, J.H.L., Raible, F., Korchagina, N., Dray, N., Samain, S., Magdelenat, G., Jubin, C., Segurens, B., Balavoine, G., Arendt, D., and Ferrier, D.E.K. Features of the ancestral bilaterian inferred from Platynereis dumerilii ParaHox genes. BMC Biology (2009) in press.

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