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Evolution of vertebrate blood vessels


Project Description

The blood vessels are the core elements of the circulatory system of animals, and their malfunction is related to most human diseases including cancer and heart attacks. The key to curing/preventing these diseases is, therefore, to understand the process of vascular formation. Despite many studies dedicated to this field, the mechanism underlying the evolution of the vertebrate vascular system remains largely unexplored. The invertebrate vessel has a much simpler structure, lacking the endothelium, and if we understand how the vertebrate vasculature system originated, it will facilitate deciphering a complex gene network to control vasculogenesis/angiogenesis in vertebrates.

To address this issue, this project will examine the molecular mechanisms of vascular formation in the basal chordates, namely tunicates (C. intestinalis) and amphioxus (B. lanceolatum). They have recently emerged as significant models for exploring the evolutionary origins of vertebrate traits based on their key phylogenetic positions and morphologic/genomic simplicity. In fact, our laboratory is currently analysing the origin of vertebrate haematopoiesis in a related project using these models. We will first clone genes homologous to vertebrate angiogenic regulatory molecules, and determine their developmental expressions in these two species. Molecular functions of these genes will be then analysed using antisense morpholino oligos and siRNA. By comparison with the data from the zebrafish model, this project aims to reveal how the vertebrate vascular system has been established during the early evolutionary history of vertebrates.

This project will use molecular, cellular and developmental techniques including isolation of genomic and cDNA clones, in situ hybridisation, embryonic manipulations and in vivo live imaging of zebrafish, as well as comparative genomics.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.

References

McGonnell, I., Graham, A., Richardson, J., Fish, J., Depew, M., Dee, C., Holland, P. & Takahashi, T (2011). Evolution of the Alx homeobox gene family: parallel retention and independent loss of the vertebrate Alx3 gene. Evol Dev, 13(4), 343-351.

Takahashi, T., McDougall, C., Troscianko, J., Chen, W., Jayaraman-Nagarajan, A., Shimeld, S. & Ferrier, D (2009). An EST screen from the annelid Pomatoceros lamarckii reveals patterns of gene loss and gain in animals. BMC Evol Biol, 9, 240.

Takahashi T. (2005). The evolutionary origins of vertebrate midbrain and MHB: insights from mouse, amphioxus and ascidian Dmbx homeobox genes. Brain research bulletin, 66(4-6), 510-7.

Holland PW, Takahashi T. (2005). The evolution of homeobox genes: Implications for the study of brain development. Brain research bulletin, 66(4-6), 484-90.

Takahashi T, Holland PW. (2004). Amphioxus and ascidian Dmbx homeobox genes give clues to the vertebrate origins of midbrain development. Development (Cambridge, England), 131(14), 3285-94.

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