The molecular basis of mesoderm formation

The different cell types of the body are formed in the right place and at the right time in response to signals that are produced by special organiser regions of the embryo. These so-called morphogens act in a concentration-dependent manner to induce the formation of different cell types at different positions within developing tissues. One of the earliest interactions of this kind is mesoderm induction, which results in the formation of organs and cell types such as heart, muscle, kidney and bone.
We use frog, zebrafish and mouse embryos to study mesoderm-inducing factors and to ask how cells respond to them. In particular we use imaging approaches to understand how the signals exert long-range effects in the embryo, as well as biochemical and mathematical approaches to ask how cells distinguish between different morphogen concentrations to activate different developmental pathways. We also use a range of molecular techniques to identify the genes that are activated by these signalling pathways and which go on to activate the genetic regulatory networks that result in the formation of specific cell types. We hope that our work will help in efforts to direct stem cells down the desired developmental pathways.
Jim Smith did his PhD with Lewis Wolpert at the MIddlesex Hospital Medical School, where he studied the development of the vertebrate limb. He then held a postdoctoral fellowship at Harvard Medical School studying the mode of action of platelet-derived growth factor, before returning to the UK to work with Dr Jonathan Slack on early amphibian development. He became a tenure-track group leader at the Medical Research Council’s National Institute for Medical Research (NIMR) in 1984, and left the Institute in 2000, as Head of the Genes and Cellular Controls Group, to become Director of the Wellcome Trust/Cancer Research UK Gurdon Institute in Cambridge. He returned to the NIMR in 2009 as Director. Jim Smith has been awarded several prizes for his work, and is a member of EMBO, a Fellow of the Royal Society, of the Academy of Medical Sciences, and of the Royal Society of Arts, and is a member of the Academia Europaea.

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