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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.


The control of segment identity by Hox genes

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.


Evolution and function of arthropod and annelid Hox clusters

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.


The evolution of segmentation mechanisms in arthropods

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. 


The control of segment number variation in centipedes

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.


Gene regulatory networks underlying head and mesoderm patterning

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


The centipede genome

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.


How to turn a wing into a haltere - Hox gene targets during metamorphosis

Hox genes are the master regulators that cause different parts of the body to develop into different structures – for example, into mouthparts on the head, but legs on the thorax. It is still not known how Hox genes bring about these complex changes.  In work published recently in the Proceedings of the National Academy of Sciences (USA), we have shown that the set of downstream targets regulated by one Hox gene changes dramatically as development proceeds.

We have studied the Hox gene Ultrabithorax, (Ubx for short) in fruit flies. In all insects, Ubx is active in the hind wings to make them different from the forewings. In flies, this difference is dramatic – the hind wings develop as small round balancing organs called halteres, while the forewings forms the large flat wing blades used for flying.   We have engineered a system that allows us to activate the Ubx gene in developing wing blades, where it would not normally be expressed. If activated throughout development, this causes the wing blades to develop as reduced balloon-like structures resembling halteres, (see picture above).  However, we can also turn Ubx on at precisely controlled times during development, and then measure its effects in the wing with assays that monitor the activity of thousands of other genes in the genome (microarray profiling and quantitative RT-PCR).

We find that the spectrum of genes regulated by Ubx changes dramatically as the animal proceeds through metamorphosis, from larva to pupa to developing adult.  This explains, at least in part, how just one gene can orchestrate such complex changes in the shape and size of an organ.

The Hox gene Ultrabithorax regulates distinct sets of target genes at successive stages of Drosophila haltere morphogenesis, PNAS USA, 108(7): 2855-2860].