Professor of Neuroscience
Roger Keynes is accepting applications for PhD students.
Development and repair of the nervous system
Repulsion of axon growth cones is an important mechanism regulating nerve 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 major clinical consequences. We have identified an axon-repulsive glycoprotein expressed on the surface of somite cells that generates the segmented pattern of spinal nerves in birds and mammals. A closely related repellent glycoprotein is expressed in the grey matter of the mature avian and mammalian brain, where we hypothesize it regulates synaptic plasticity and may contribute to CNS regenerative failure. Besides elucidating the molecular biology of this system, its function and its mechanism, an important clinical aim is to block its inhibitory action using models of brain and spinal cord injury, to see whether improved functional regeneration can be achieved.
The vertebral column defines the vertebrates, yet it remains unknown how the patterning of its embryonic progenitors, the somites, is related to mature vertebrae. The vertebral repeat pattern in amniotes (reptiles, birds and mammals) has been suggested to develop by a process of resegmentation, when the neighbouring halves of adjacent somites unite to form each vertebra. Our recent experiments support this mechanism, but we also have evidence that in teleost fish (zebrafish) the pattern is generated via midline signals from the notochord. This has interesting implications for the evolution of vertebral patterning, and is being assessed further in the zebrafish with Dr Angeleen Fleming (Department PDN, Cambridge).
Geoffrey Cook (Department of Physiology, Development & Neuroscience)
James Fawcett (Cambridge Centre for Brain Repair)
Chuck Kimmel (Institute of Neuroscience, Oregon)
Claudio Stern (University College, London)
David Tannahill (Cancer Research UK Cambridge Institute)
Building the backbone: the development and evolution of vertebral patterning, Development, 142: 1733-1744 doi:10.1242/dev.118950
Manns R, Schmandke A, Schmandke A, Jareonsettasin P, Cook G, Schwab ME, Holt C, Keynes R, (2014), Protein synthesis dependence of growth cone collapse induced by different Nogo-A-domains, PLoS One, 10.1371 journal.pone.0086820
Cook GMW, Jareonsettasin P, Keynes R, (2014), Growth cone collapse assay, in Axon Growth and Regeneration: Methods and Protocols Methods in Molecular Biology, vol. 1162, Humana Press, Springer Science and Business Media, New York
Manns RPC, Cook GMW, Holt CE, Keynes RJ, (2013), Differing Semaphorin 3A concentrations trigger distinct signaling mechanisms in growth cone collapse, Journal of Neuroscience, 32: 8554-8559
Muir E, Keynes R, (2013), Prospects for Spinal Cord Repair, in Disorders of the spinal cord in children, (ed. MG Pike) Clinics in Developmental Medicine, Mac Keith Press
Senthinathan B, Sousa C, Tannahill D, Keynes R, (2012), The generation of vertebral segmental patterning in the chick embry, Journal of Anatomy, 220: 591–602