Dr Seb Shimeld

Research projects

· Evolution of gene networks and the origin of vertebrates

· Fox genes in animal evolution

· Evolution of left-right asymmetry

· Gene duplication, divergence and gene family evolution

· Developmental biology of protostomes and bilaterian origins

Evolution of gene networks and the origin of vertebrates

At both the genetic and morphological level vertebrates are more complicated than their invertebrate relatives. Vertebrates appear to have invented a number of new tissues, such as the neural crest and placodes, and to have massively elaborated others, such as the brain. They also have more regulatory genes than their invertebrate relatives, with most families of transcription factor and signalling molecule genes having expanded by gene duplication during early vertebrate evolution. We are investigating how both molecular and morphological complexity has evolved. Using molecular and embryological methods we are characterising the development of animals such as ascidians, amphioxus and lampreys (see Fig. 1), lineages of living creatures which span the origin of vertebrates. A special emphasis is placed on unravelling the changing roles of regulatory gene networks involved in the development of vertebrate specific morphology. Within this broad area several specific research projects are underway, including:

• The evolution of the vertebrate lens and crystallin genes
• The evolutionary origin of placodes
• The evolution of enhancer and promoter structure
• The evolutionary diversification of vertebrate mesoderm

Fig. 1 (above):To the left is the head of an ascidian tadpole larva, showing the two pigmented cells that help mediate sensation of gravity and light. To the right is an adult amphioxus. The head is to the left and the numerous gill bars are visible behind the tentacular cirri that surround the mouth. Both pictures by Seb Shimeld.

Recent publications in this area:

Shimeld, S.M. and Donoghue, P.J. (2012) Evolutionary crossroads in developmental biology: cyclostomes (lamprey and hagfish). Development 139: 2091-2099.

Graham, A. and Shimeld, S.M. (2012). The origin and evolution of the ectodermal placodes. J. Anat. In press.

Shimeld, S.M., van den Heuvel, M., Dawber, R. and Briscoe, J. (2007) An Amphioxus Gli Gene Reveals Conservation of Midline Patterning and the Evolution of Hedgehog Signalling Diversity in Chordates. PLoS One.

Riyahi, K. and Shimeld, S.M. (2007). Chordate beta-gamma crystallins and the evolutionary developmental biology of the vertebrate lens. Comp Biochem Physiol B 147: 347-357.

Shimeld, S.M., Purkiss, A.G., Dirks, R.P.H., Bateman, O.A, Slingsby, C. and Lubsen, N.H. Urochordate βγ-crystallin and the evolutionary origin of the vertebrate eye lens. Current Biology, 15: 1684-1689. PDF

Mazet, F., Hutt, J.A., Milloz, J., Millard, J., Graham, A. and Shimeld, S.M. (2005). Molecular evidence from Ciona intestinalis for the evolutionary origin of vertebrate sensory placodes. Dev Biol 282: 494-508. PDF.

Mazet, F. and Shimeld, S.M. (2005) Evolutionary origin of vertebrate cranial sensory placodes. J Exp Zool B Mol Dev Evol 304B: 340-346. PDF

Shimeld, S.M. and Holland, N.D. (2005) Amphioxus molecular biology: insights into vertebrate evolution and developmental mechanisms. Can J Zool 83: 90-100. PDF

Mazet, F. Masood, S., Luke, G.N., Holland, N.D. and Shimeld, S.M. (2004) Expression of AmphiCoe, an amphioxus COE/EBF gene, in the developing central nervous system and epidermal sensory neurons. Genesis 38: 58-65. PDF

Mazet, F. and Shimeld, S.M. (2003) Characterisation of an amphioxus Fringe gene and the evolution of the vertebrate segmentation clock. Dev Genes Evol.213: 505-509. PDF

Gostling, N.J. and Shimeld, S.M. Protochordate Zic genes define primitive somite compartments and highlight molecular changes underlying neural crest evolution. Evol Dev5: 136-144. PDF

Mazet, F. and Shimeld, S.M. (2002) The evolution of chordate neural segmentation Dev Biol 251: 258-270. PDF

Boorman, C.J.  and Shimeld, S.M. (2002) Cloning and expression of a Pitx homeobox gene from the lamprey, a jawless vertebrate. Dev Genes Evol 212: 349-353. PDF

Knight, R.D., Panopoulou, G.D., Holland, P.W.H. and Shimeld, S.M. (2000). An amphioxus Krox gene: Insights into vertebrate hindbrain evolution. Dev Genes Evol 210: 518-521. PDF

Shimeld, S.M. (2000). An amphioxus netrin gene is expressed in midline structures during embryonic and larval development. Dev Genes Evol 210: 337-344. PDF

Comparative Genomics of Fox genes and animal evolution

The Fox genes encode transcription factors of the winged helix type. There are about 46 members of this family in the human genome, with less identified in the genomes of invertebrates. My interests in these genes stems from three sources:

• To establish orthology and paralogy relationships between Fox genes from different Phyla, to identify and time gene duplications.
• To investigate their role in the development and differentiation of different types of mesoderm.
• To establish their relative position in animal genomes to investigate linkage and the evolution of gene clusters (e.g. Figure 2)

A specific focus are Fox genes of the FoxF, FoxC, FoxL1 and FoxQ1 classes, which my collaborators and I have shown are clustered in several animal genomes. Together with Professor Bernie Degnan (Brisbane) and Dr Elaine Seaver (Kewalo marine Lab, Hawaii) we have exploited the sequencing of a multitude of invertebrate genomes to perform a comprehensive study of these genes and as a springboard for further expression and functional studies.

Figure 2 (above): Fox cluster organisation in a selection of animal genomes

Recent publications in this area:

Paps, J., Holland, P.W.H., Shimeld, S.M. (2012). A genome-wide view of transcription factor gene diversity in chordate evolution: less gene loss in amphioxus? Briefings in Functional Genomics 11: 177-186.

Wotton, K. and Shimeld, S.M. (2011). Analysis of lamprey clustered Fox genes: Insight into Fox gene evolution and expression in vertebrates. Gene 489: 30-40.

Shimeld, S.M., Boyle, M.J., Brunet, T., Luke, G.N. and Seaver, E.C. (2010). Clustered Fox genes in lophotrochozoans and the evolution of the bilaterian Fox gene cluster. Dev. Biol. 240: 234-248.

Shimeld, S.M., Degnan, B. and Luke, G.N. (2010). Evolutionary genomics of the Fox genes: Origin of gene families and the ancestry of gene clusters. Genomics. 95: 256-260.

Yu, J.-K., Mazet, F., Chen, Y.-T., Huang, S.-W., Jung, K.-C. and Shimeld, S.M. (2008) The Fox genes of Branchiostoma floridae. Dev Genes Evol 218: 629-638.

Larroux, C., Luke, G.N., Koopman, P., Rokhsar, D.S., Shimeld, S.M. and Degnan, B.M. (2008). Genesis and expansion of metazoan transcription factor gene classes Mol Biol Evol 25:980-96.

Wotton, K, Mazet, F. and Shimeld, S.M. (2008). Expression of FoxC, FoxF, FoxL1, and FoxQ1 genes in the dogfish Scyliorhinus canicula defines ancient and derived roles for Fox genes in vertebrate development. Dev Dynamics 237:1590-1603.

Wotton, K. and Shimeld, S.M. (2006). Comparative genomics of vertebrate Fox cluster loci. BMC Genomics doi:10.1186/1471-2164-7-271. PDF.

Mazet, F., Amemiya, C. and Shimeld, S. M. (2006). An ancient Fox gene cluster in the Bilateria. Current Biology 16: R314-R316. PDF.

Mazet, F., Luke, G.N. and Shimeld, S.M. (2005) An amphioxus FoxQ1 gene is expressed in the developing endostyle. Gene Expression Patterns 5: 313-315. PDF.

Mazet, F., Yu, J.-K., Liberles, D., Holland, L.Z. and Shimeld, S.M. (2003). Phylogenetic relationships of the Fox (forkhead) gene family in the Bilateria. Gene. 316: 79-89. PDF

Yagi, K., Satou, Y, Mazet, F., Shimeld, S.M., Degnan, B., Rokhsar, D, Levine, M., Kohara, Y. and Satoh, N. (2003). A genomewide survey of developmentally relevant genes in Ciona intestinalis III. Genes for Fox, ETS, nuclear receptors and NFκB. Dev. Genes Evol. 213: 235-244.

Evolution of left-right asymmetry

Vertebrates are superficially symmetric, but internally their organs are asymmetrically distributed. This is controlled by a conserved molecular pathway including the Pitx homeobox gene family and the Nodal family of signalling molecules. We have been tracing the evolutionary origin of this pathway, and have shown that all chordates have both asymmetric morphology and asymmetrically localised gene expression.  Future work has investigated the early establishment of asymmetry in chordates and protostome invertebrates, and the role of intercellular communication in this process.

Fig. 3 (above : Asymmetric expression of Pitx genes in an ascidian (left) and amphioxus (centre) and a vertebrate(right). In all three taxa the gene is localised in on the left side of the embryo. For more details see Boorman and Shimeld (2002).

Recent publications in this area:

Thompson, H., Shaw, M.K., Dawe, H. and Shimeld, S.M. (2012). The formation and positioning of cilia in Ciona intestinalis embryos in relation to the generation and evolution of chordate left-right asymmetry. Dev. Biol. 364: 214-223.

Shimeld, S. M. and Levin, M. (2006). Evidence for the regulation of left-right asymmetry in Ciona by ion flux. Dev Dynamics 235: 1543-1553. PDF.
Shimeld, S.M. (2004). Calcium turns sinister in left-right asymmetry. Trends Genet 20: 277-280. PDF
Boorman, C.J.  and Shimeld, S.M. (2002) Cloning and expression of a Pitx homeobox gene from the lamprey, a jawless vertebrate. Dev Genes Evol 212: 349-353. PDF
Boorman, C.J.  and Shimeld, S.M. (2002) Pitx homeobox genes in Ciona and amphioxus show left-right asymmetry is a conserved chordate character and define the ascidian adenohypophysis. Evol Dev 4: 354-365. PDF
Boorman, C.J. and Shimeld, S.M. (2002) The evolution of chordate left right asymmetry. Bioessays 24: 1004-1011. PDF

Gene duplication, divergence and gene family evolution

The duplication of genes is of common occurrence in evolution. For example early vertebrate evolution is marked by widespread gene duplication resulting from duplication of the entire genome. We are using molecular phylogenetic approaches coupled with cloning genes from specific, key taxa to reconstruct the evolution of complex gene families. Current projects focus on the Fox transcription factor family and the C2H2 zinc finger genes, an enormous family with over 1000 members in the human genome. Our aim is to identify when gene duplications have occurred and how genes have diverged, and subsequently to investigate the role of this in morphological evolution.

Fig. 4 (above): A model for transcription factor gene divergence in early animal evolution. See Larroux et al (2008) for more details.

Recent publications in this area:

Paps, J., Holland, P.W.H., Shimeld, S.M. (2012). A genome-wide view of transcription factor gene diversity in chordate evolution: less gene loss in amphioxus? Briefings in Functional Genomics 11: 177-186.

Larroux, C., Luke, G.N., Koopman, P., Rokhsar, D.S., Shimeld, S.M. and Degnan, B.M. (2008). Genesis and expansion of metazoan transcription factor gene classes Mol Biol Evol 25:980-96.

Shimeld, S.M. (2008). C2H2 zinc finger genes of the Gli, Zic, KLF, SP, Wilms’ tumour, Huckebein, Snail, Ovo, Spalt, Odd, Blimp-1, Fez and related gene families from Branchiostoma floridae. Dev Genes Evol 218: 639-649.

Shimeld, S.M., van den Heuvel, M., Dawber, R. and Brisco, J. (2007) An Amphioxus Gli Gene Reveals Conservation of Midline Patterning and the Evolution of Hedgehog Signalling Diversity in Chordates. PLoS One.

Mazet, F., Yu, J.-K., Liberles, D., Holland, L.Z. and Shimeld, S.M. (2003). Phylogenetic relationships of the Fox (forkhead) gene family in the Bilateria. Gene. 316: 79-89. PDF

Yagi, K., Satou, Y, Mazet, F., Shimeld, S.M., Degnan, B., Rokhsar, D, Levine, M., Kohara, Y. and Satoh, N. (2003). A genomewide survey of developmentally relevant genes in Ciona intestinalis III. Genes for Fox, ETS, nuclear receptors and NFκB. Dev. Genes Evol. 213: 235-244.

Mazet, F. and Shimeld, S.M. (2002) Gene duplication and divergence in the early evolution of vertebrates. Curr Opin Genet Dev 12: 393-396. PDF

Knight, R.D. and Shimeld, S.M. (2001). Identification of conserved C2H2 zinc finger gene families in the Bilateria. Genome Biology 2: 0016.1-0016.8. PDF

Sedlacek, Z., Shimeld, S.M., Münstermann, E. and Poustka, A. (1999). The amphioxus rabGDI gene is neural specific: Implications for the evolution of chordate rabGDI genes. Mol Biol Evol 16: 1231-1237. PDF

Developmental biology of protostomes and bilaterian origins

Most living animals, including vertebrates, are members of the Bilateria, a group of animals that are primitively bilaterally symmetrical. Our current understanding of the development and genomics of bilaterian animals comes primarily from a rather small number of taxa, representing two of the three superphyletic clades that constitute the Bilateria. The third clade, the Lophotrochozoa, includes the annelids and molluscs, and is much understudied at both the developmental and genomic levels. We are investigating several aspects of genome organisation and development of the polychaete annelid Pomatoceros lamarckii and the mollusc Patella vulgata. Our long-term aim is to use this data to reconstruct the developmental and genomic complexity of the common ancestor of the Bilateria, and gain insight into the origins of this group of animals. Towards this aim we have developed genome sequences and transcriptomes for these species, coupled with methods for studying gene expression and manipulating gene function. Associated with this we have also started to investigate the

Fig. 5 (above) :To the left is an adult serpulid polychaete Pomatoceros lamarckii. In the centre is a P. Lamarckii larva and to the right a Patella vulgata embryo stained for Fox gene expression.

Recent publications in this area:

Shimeld, S.M., Boyle, M.J., Brunet, T., Luke, G.N. and Seaver, E.C. (2010). Clustered Fox genes in lophotrochozoans and the evolution of the bilaterian Fox gene cluster. Dev. Biol. 240: 234-248.

Takahashi, T., McDougall, C., Troscianko, J., Chen, W.C., Jayaraman-Nagarajan, A., Shimeld, S.M. and Ferrier, D.E.K. (2009) An EST screen from the annelid Pomatoceros lamarckii reveals patterns of gene loss and gain in animals. BMC Evol. Biol. 9: 240. See a review of this paper in the Journal of Biology

McDougall, C., Chen, W.-C., Shimeld, S.M. and Ferrier, D.E.K. (2006). The development of the larval nervous system, musculature and ciliary bands of Pomatoceros lamarckii (Annelida): heterochrony in polychaetes. Frontiers in Zoology doi:10.1186/1742-9994-3-16. PDF.