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Prof Roger Keynes

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Professor
Tel: +44 (0)1223 333760, Fax: +44 (0)1223 333786, E-mail: rjk10@cam.ac.uk

1) Development and repair of the nervous system
Growth cone repulsion is an important mechanism controlling axon growth. During development it guides axons by excluding them from "no-go" areas in the embryo. Following injury to the adult brain it may also block axon regeneration, with serious clinical consequences. Our laboratory is investigating 3 axon-repulsive systems where the underlying mechanisms can be studied at the molecular level. First, we are characterizing glycoproteins on the surface of chick somite cells that repel axons and that create the segmented pattern of spinal nerves during development. Second, we have identified repulsive proteins secreted by the embryonic notochord that orient primary sensory axons in the dorso-ventral axis of the embryo. We have also purified a repulsive protein in the grey matter of the adult avian and mammalian brain; we hypothesize that such proteins have evolved to regulate synaptic plasticity, perhaps contributing to CNS regenerative failure. Besides elucidating the molecular biology of these molecules and their receptors, an important clinical aim will be to interfere with their inhibitory action using models of brain and spinal cord injury, to see whether improved functional regeneration can be achieved. See also www.pubs.royalsoc.ac.uk/axon-guidance

2) Vertebral segmental patterning
The vertebral column defines all vertebrates, yet it is unknown how the patterning of its embryonic progenitors, the somites, is related to mature vertebrae. The vertebral repeat pattern has been suggested to develop by a "resegmentation" mechanism, when the neighbouring halves of adjacent somites unite together. Alternatively, however, the pattern may be generated via midline signals from the notochord, and we have good evidence for this in the zebrafish. We are now investigating the role of the notochord in vertebral segmentation of higher vertebrates, using the chick embryo as a model system.

Colleagues
Dr Geoff Cook (Department of Anatomy)
Dr Kelly Kuan (Research Associate)
Dr Liz Muir (Research Associate)
Mr Dan Hughes (Graduate Student)
Mr Spike Lo (Graduate Student)
Ms Julie Ghosh (Graduate Student)
Mrs Christine Turner (Technician)
Mrs Keily Littlefield (Technician)

Main Collaborators
David Tannahill (Sanger Institute, Cambridge)
James Fawcett (Cambridge Centre for Brain Repair)
Claudio Stern (University College, London)
Elizabeta Mukaetova-Ladinska (Newcastle)
Adrian Pini (King's College, London)
Kunimasa Ohta (Kumamoto University, Japan)

Main Sources of Funding: MRC

Selected Publications
Keynes RJ, Tannahill D, Morgenstern DA, Johnson AR, Cook GMW & Pini A (1997) Surround-repulsion of sensory axons in higher vertebrate embryos. Neuron 18, 889-897 (ref.)

Cook GMW, Tannahill D & Keynes RJ (1998) Axon guidance to and from choice points. Current Opinion in Neurobiology 8, 64-72 (ref.)

Ohta K, Tannahill D, Yoshida K, Johnson AR, Cook GMW & Keynes RJ (1999) Embryonic lens repels retinal ganglion cell axons. Developmental Biology 211, 124-132 (ref.)

Vermeren MM, Cook GMW, Johnson AR, Keynes RJ & Tannahill D (2000) Spinal nerve segmentation in the chick embryo: analysis of distinct axon-repulsive systems. Developmental Biology 225, 241-252 (ref.)

Britto, J, Tannahill D & Keynes R (2002) A critical role for sonic hedgehog signaling in the early expansion of the developing brain. Nature Neuroscience 5, 103-110 (ref.)

Anderson CNG, Ohta K, Quick MM, Fleming A, Keynes R & Tannahill D (2003) Molecular analysis of axon repulsion by the notochord. Development 130, 1123-1133 (ref.)

Fleming A, Keynes R & Tannahill D. (2004) A central role for the notochord in vertebral patterning. Development 131, 873-80 (ref.)

Kuan C-YK, Tannahill D, Cook GMW & Keynes RJ (2004) Somite polarity and segmental patterning of the peripheral nervous system. Mechanisms of Development 121, 1055-1068 (ref.)