Selected publications

• Ciau-Uitz A, Walmsley M, and Patient R (2000) Distinct origins of adult and embryonic blood in Xenopus. Cell, 102(6):787-96.

• Gering Martin and Patient Roger (2005) Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos. Dev Cell, 8(3):389-400.

• Liu Feng, Walmsley Maggie, Rodaway Adam, and Patient Roger (2008) Fli1 acts at the top of the transcriptional network driving blood and endothelial development. Curr Biol, 18(16):1234-40.

• Peterkin Tessa, Gibson Abigail, and Patient Roger (2009) Common genetic control of haemangioblast and cardiac development in zebrafish. Development, 136(9):1465-74.

• Wilkinson Robert N, Pouget Claire, Gering Martin, Russell Angela J, Davies Stephen G, Kimelman David, and Patient Roger (2009) Hedgehog and Bmp polarize hematopoietic stem cell emergence in the zebrafish dorsal aorta. Dev Cell, 16(6):909-16.

Prof Roger Patient

Cells are programmed during embryonic development. As they move through the embryo, they receive signals from neighbouring cells thereby establishing their gene expression programmes. The agents of this programming are transcription factors whose expression is initially controlled by the embryonic signals and therefore by other transcription factors. Transcriptional regulatory networks are established, which become independent of the initiating signals but may remain dependent on maintenance signalling. Thus, as cells differentiate and arrive in their niches, their networks become stabilised. Understanding how these networks are established and maintained is the main interest of our lab. Our focus is on blood and the cardiovascular system. We have a particular interest in the programming of blood stem cells, an understanding of which will inform our understanding of many diseases including leukaemias. For example, genetic and environmental insults can be modelled and both the consequences and actions that might induce recovery can be predicted. In addition, realising the potential of stem cells to repair damaged or lost tissue will depend on the ability to manipulate these cells which in turn will benefit from a better understanding of these molecular circuitries.

We are studying these processes in amphibia and fish (Xenopus and zebrafish), whose embryos are laid in large numbers and develop externally. Techniques have been developed to manipulate signalling regimes and transcription factor activities in these embryos as they develop. Methodologies include genetic mutations, antisense depletion, mRNA injection, transgenesis, dominant negative expression and small molecule inhibition. The consequences of perturbation for the expression of large numbers of genes can readily be determined using automated in situ hybridisation. Cell lineages have been traced enabling targeted perturbations. In addition, we have the capacity to study development in embryo explants to simplify development in defined conditions. In these ways, we are defining how embryos programme blood and the cardiovascular system, and we are recapitulating these processes in vitro.

Blood stem cells (purple) emerging in the floor of the dorsal aorta independently of the circulating primitive red cells in zebrafish embryos