Our diverse interests all relate to different aspects of a few key questions: How does a largely conserved set of genes in all animal species generate the extraordinary diversity that we see in body form and embryological development? Which aspects of gene function and developmental process are widely conserved between the most distantly related animals, and which are highly variable even between rather closely related species. Can we link innovtions in the genome to changes in body plans or life history strategies. To study these questions, we use a diversity of techniques, but particularly the approaches of genomics, genetics and comparative molecular embryology.
Hox genes encode developmental regulators that tell cells where they are in the embryo. If they are turned on or off inappropriately, structures develop in the wrong place - a leg may form where the antenna should be, or in the case of our favourite Hox gene, Ubx, a wing may turn into a small balancing organ. Just how a single regulatory gene can transform the development of a whole complex organ is not well understood. Working with Drosophila, we study the set of targets regulated by the Hox gene Ubx, and how these transform the morphology of one organ into another.
Pavlopoulos, A. and Akam, M. (2011). The Hox gene Ultrabithorax subtly regulates distinct sets of target genes at successive stages of haltere morphogenesis and differentiation. Proc. Natl. Acad. Sci. USA B in press. (doi:10.1073/pnas.1015077108)
Reed, H.C., Hoare, T., Thomsen, S., Weaver, S., Akam, M. and Alonso, C. (2010) Alternative splicing modulates Ubx protein function in Drosophila melanogaster. Genetics 184, 745-758.
Pavlopoulos, A. and Akam, M. (2007) Hox go omics: Insights from Drosophila on Hox gene function. Genome Biology 8, 208.
Hox genes are widely conserved across the animal kingdom, but changes in the way that Hox genes are used play an important role in generating the diversity of body plans seen among arthropods. We study the evolution of novel Hox-derived genes, the role of Hox genes in generating the diversity of segment morphologies in crustaceans, and the functional organisation of the Hox cluster in a centipede, where antisense transcripts may play a role in the localisaton of Hox gene function
Pavlopoulos, A., Kontarakis, Z., Liubicich, D. M., Serano, J. M., Akam, M., Patel, N. H. and Averof, M. (2009) Probing the evolution of appendage specialisation by Hox gene misexpression in an emerging model crustacean. Proc. Natl. Acad. Sci. USA 106, 13897-13902.
Liubicich, D. M., Serano, J. M., Pavlopoulos, A., Kontarakis, Z., Protas, M. E., Kwan, E., Chatterjee, S., Tran, K. D., Averof, M. and Patel, N. H. (2009). Knockdown of Parhyale Ultrabithorax recapitulates evolutionary changes in crustacean appendage morphology. Proc. Natl. Acad. Sci. USA 106, 13892-13896.
Panfilio, K. and Akam, M. (2007) A comparison of Hox3 and Zen protein coding sequences in taxa that span the Hox3/ zen divergence. Dev. Genes. Evol. 217, 323-349.
Kulakova, M., Bakalenko, N., Novikova, E., Cook, C. E., Eliseeva, E., Steinmetz, P., Kostyuchenko, R. P., Dondua, A., Arendt, D., Akam, M. and Andreeva, T. (2007) Hox gene expression in larval development of the polychaetes Nereis virens and Platynereis dumerilii (Annelida, Lophotrochozoa. Dev. Genes. Evol.. 217, 39-54.
Brena, C., Chipman, A. D., Minelli, A. and Akam, M. (2006) The expression of trunk Hox genes in the centipede Strigamia maritima: Sense and antisense transcripts. Evol. Dev. 8, 252-265.
Arthropods share with vertebrates the characteristic that they divide their body into a series of similar but distinct structural units, termed segments. In ourselves these segments generate the series of vertebrae that make up our back; in arthropods, they form the distinct units of the articulated external skeleton. It is understoond rather well how segments are made in the fruit fly Drosophila, but there are good reasons to believe that the process of segmentation has evolved within the arthropods such that an ancestral clock like mechanism which added segments one at a time has been replaced by one that allows all the segments to be generated simultaneously. We study a range of species to understand how the gene networks that underlie the process of segmentation have changed to make this possible.
Garcia-Solache, M., Jaeger, J. and Akam, M. (2010) A systematic analysis of the gap gene system in the moth midge Clogmia albipunctata. Dev. Biol. 344, 306-318
Eriksson, B. J., Tait, N. N., Budd, G. E., and Akam, M. (2009) The involvement of engrailed and wingless during segmentation in the onychophoran Euperipatoides kanangrensis (Peripatopsidae: Onychophora) (Reid 1996). Dev. Genes Evol. 219, 249-264.
Chipman, A. D. and Akam, M. (2008) The segmentation cascade in the centipede Strigamia maritima: Involvement of the Notch pathway and pair-rule gene homologues. Dev. Biol. 319, 160-169.
Peel, A. D., Telford, M.J. and Akam, M. (2006) The evolution of hexapod engrailed-family genes: Evidence for conservation and concerted evolution. Proc. Roy. Soc. Lond. B 273, 1733-1742.
Peel, A. D., Chipman, A. D. and Akam, M. (2005). Arthropod segmentation: Beyond the Drosophila paradigm. Nature Rev. Genet. 6, 905-916.
In the centipede species we study, Strigamia maritima, the number of segments generated during embryogenesis is variable between individuals of the population, and between different populations. This is rather unusual in living arthropods, but such variability must underlie the great diversity in segment number that characterises the many different arthropod species alive today. In collaboration with the group of Wallace Arthur (National University of Ireland, Galway), we are studying the developmental and genetic mechanisms that account for the differences in segment number between individuals, and populations
Vedel, V., Apostolou, Z., Arthur, W., Akam, M. and Brena, C. (2010) An early temperature sensitive period for the variation in segment number in the centipede Strigamia maritima. Evolution and Development 12, 347-352.
Vedel, V., Brena, C. and Arthur, W. (2009) Demonstration of a heritable component of the variation in segment number in the centipede Strigamia maritima. Evol. Dev. 11, 434-440.
Vedel, V., Chipman, A. D., Akam, M. and Arthur, W. (2008) Temperature dependent plasticity of segment number in an arthropod species: the centipede Strigamia maritima. Evolution and Development 104, 487-492.
Through the Marie Curie Initial Training Network "Evonet' we are participating in a collaboration to examine, across the animal kingdom, the conservation and diversity of the mechanisms that pattern the most anterior regions of the animal body, including the brain, and the internal tissues of the blood, muscles, and gonads, all of which derive from an embryonic tissue layer called the mesoderm. We focus on basal arthropod lineages (centipedes, onychophorans), which may retain aspect of ancestral patterning mechanisms that have been lost in the well studied flies and other higher insects.
Steinmetz, P. R. H., Urbach, R., Posnien, N., Eriksson, J., Kostyuchenko, R. P., Brena, C., Guy, K., Akam, M., Bucher, G. and Arendt, D. (2010) Six3 demarcates the anterior-most developing brain region in bilaterian animals. Evo-Devo 1, 14.
Eriksson, J., Tait, N. N., Budd, G. E., Janssen, R. and Akam, M. (2010) Head patterning and Hox gene expression in an onychophoran and its implications for the arthropod head problem. Dev. Genes Evol. 22, 117-122
New data on the relationships of living arthropods make it clear that the myriapods - the group including millipedes and centipedes - are an ancient lineage of arthropods, probably the first to invade the land, and sister lineage to all of the insects and crustaceans. Studies of this neglected group promise to tell us much about the history of arthropods, and the nature of their last common ancestor. Strigamia maritima was selected as the first myriapod to have its genome completely sequenced, and the sequencing was completed in 2010. We are coordinating a group to annotate the sequence, identifying which genes have been gained, which lost, and how they have been reorganised in the 400 million years of evolution that separate this genome from the genome of its nearest sequenced relatives.