Professor Roger Keynes University positionProfessor Professor Roger Keynes is pleased to consider applications from prospective PhD students. DepartmentsDepartment of Physiology, Development and Neuroscience Home pagehttp://www.pdn.cam.ac.uk/staff/k... Research ThemesInterestsGrowth cone repulsion is an important mechanism controlling axon growth. During development it guides axons by excluding them from repulsive regions of the embryo. Following injury to the adult brain it may also block axon regeneration, with major clinical consequences. Our laboratory is investigating two axon-repulsive systems. We are characterizing somite glycoproteins that repel axons, creating the segmented pattern of spinal nerves during development. We have also purified a repulsive protein in the grey matter of the adult brain that may contribute to CNS regenerative failure. Besides elucidating the biology of these molecules and their receptors, an important clinical aim is to interfere with their inhibitory action, including the use of engineered bacterial chondroitinase, to see whether improved functional regeneration can be achieved using models of brain and spinal cord injury.  Motor nerves growing out of the spinal cord during development traverse only the anterior (right) half-somites and are repelled from the posterior (left) halves. The somite boundaries are visible to the right of each of three nerve bundles. Click image to view full-size Research Focus
EquipmentCell culture Confocal microscopy Embryo manipulation Fluorescence microscopy Immunohistochemistry Microscopy Protein purification Recombinant protein expression Collaborators
Associated News ItemsKey publicationsManns RP, Cook GM, Holt CE, Keynes RJ (2012), “Differing semaphorin 3A concentrations trigger distinct signaling mechanisms in growth cone collapse.” J Neurosci 32(25):8554-9 Details DST Hughes, RJ Keynes & D Tannahill (2009), “Extensive molecular differences between anterior- and posterior-half-sclerotomes underlie somite polarity and spinal nerve segmentation” BMC Developmental Biology 2009, 9:30 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 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 Keynes R, Tannahill D, Morgenstern DA, Johnson AR, Cook GM, Pini A (1997), “Surround repulsion of spinal sensory axons in higher vertebrate embryos.” Neuron 18(6):889-97 Details Davies JA, Cook GM, Stern CD, Keynes RJ (1990), “Isolation from chick somites of a glycoprotein fraction that causes collapse of dorsal root ganglion growth cones.” Neuron 4(1):11-20 Details Fraser S, Keynes R, Lumsden A (1990), “Segmentation in the chick embryo hindbrain is defined by cell lineage restrictions.” Nature 344(6265):431-5 Details Keynes R, Cook G (1990), “Cell-cell repulsion: clues from the growth cone?” Cell 62(4):609-10 Details Lumsden A, Keynes R (1989), “Segmental patterns of neuronal development in the chick hindbrain.” Nature 337(6206):424-8 Details Stern CD, Keynes RJ (1987), “Interactions between somite cells: the formation and maintenance of segment boundaries in the chick embryo.” Development 99(2):261-72 Details Stern CD, Sisodiya SM, Keynes RJ (1986), “Interactions between neurites and somite cells: inhibition and stimulation of nerve growth in the chick embryo.” J Embryol Exp Morphol 91:209-26 Details Rickmann M, Fawcett JW, Keynes RJ (1985), “The migration of neural crest cells and the growth of motor axons through the rostral half of the chick somite.” J Embryol Exp Morphol 90:437-55 Details Keynes RJ, Stern CD (1984), “Segmentation in the vertebrate nervous system.” Nature 310(5980):786-9 Details Publications2014Manns 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 9(1):e86820 Details 2012Senthinathan B, Sousa C, Tannahill D, Keynes R (2012), “The generation of vertebral segmental patterning in the chick embryo.” J Anat 220(6):591-602 Details 2011Zhao RR, Muir EM, Alves JN, Rickman H, Allan AY, Kwok JC, Roet KC, Verhaagen J, Schneider BL, Bensadoun JC, Ahmed SG, Yáņez-Muņoz RJ, Keynes RJ, Fawcett JW, Rogers JH (2011), “Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axons.” J Neurosci Methods 201(1):228-38 Details 2010Muir EM, Fyfe I, Gardiner S, Li L, Warren P, Fawcett JW, Keynes RJ, Rogers JH (2010), “Modification of N-glycosylation sites allows secretion of bacterial chondroitinase ABC from mammalian cells.” J Biotechnol 145(2):103-10 Details 2007Naidu M, Kuan CY, Lo WL, Raza M, Tolkovsky A, Mak NK, Wong RN, Keynes R (2007), “Analysis of the action of euxanthone, a plant-derived compound that stimulates neurite outgrowth.” Neuroscience 148(4):915-24 Details 2006G Cook, J Fawcett, R Keynes & M Tessier-Lavigne (Eds) (2006), “The regenerating brain” Phil Trans Roy Soc B 361, 1459-1461 Grotmol S, Kryvi H, Keynes R, Krossøy C, Nordvik K, Totland GK (2006), “Stepwise enforcement of the notochord and its intersection with the myoseptum: an evolutionary path leading to development of the vertebra?” J Anat 209(3):339-57 Details Larner AJ, Keynes RJ (2006), “Neuroinhibitory molecules in Alzheimer's disease.” J Alzheimers Dis 10(1):75-80 Details 2005Tannahill D, Harris LW, Keynes R (2005), “Role of morphogens in brain growth.” J Neurobiol 64(4):367-75 Details 2004Fleming A, Keynes R, Tannahill D (2004), “A central role for the notochord in vertebral patterning.” Development 131(4):873-80 Details Ohta K, Lupo G, Kuriyama S, Keynes R, Holt CE, Harris WA, Tanaka H, Ohnuma S (2004), “Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin.” Dev Cell 7(3):347-58 Details 2003Anderson CNG, Ohta K, Quick MM, Fleming A, Keynes R, Tannahill D (2003), “Molecular analysis of axon repulsion by the notochord” Development 130:1123-1133 2001Fleming A, Keynes RJ, Tannahill D (2001), “The role of the notochord in vertebral column formation.” J Anat 199(Pt 1-2):177-80 Details Kimmel CB, Miller CT, Keynes RJ (2001), “Neural crest patterning and the evolution of the jaw.” J Anat 199(Pt 1-2):105-20 Details Richardson M, Keynes R, Mabee P, Selwood L (2001), “Founding editorial: embryology--an integrated approach.” ScientificWorldJournal 1:602-4 Details 2000Britto JM, Tannahill D, Keynes RJ (2000), “Life, death and Sonic hedgehog.” Bioessays 22(6):499-502 Details Gavazzi I, Stonehouse J, Sandvig A, Reza JN, Appiah-Kubi LS, Keynes R, Cohen J (2000), “Peripheral, but not central, axotomy induces neuropilin-1 mRNA expression in adult large diameter primary sensory neurons.” J Comp Neurol 423(3):492-9 Details Keynes R, Kirik D, Nieto-Sampedro M (2000), “European neuroscience meets the snow.” Trends Neurosci 23(3):91-2 Details Tannahill D, Britto JM, Vermeren MM, Ohta K, Cook GM, Keynes RJ (2000), “Orienting axon growth: spinal nerve segmentation and surround-repulsion.” Int J Dev Biol 44(1):119-27 Details Vermeren MM, Cook GM, Johnson AR, Keynes RJ, Tannahill D (2000), “Spinal nerve segmentation in the chick embryo: analysis of distinct axon-repulsive systems.” Dev Biol 225(1):241-52 Details 1999Ohta K, Tannahill D, Yoshida K, Johnson AR, Cook GM, Keynes RJ (1999), “Embryonic lens repels retinal ganglion cell axons.” Dev Biol 211(1):124-32 Details 1998Cook G, Tannahill D, Keynes R (1998), “Axon guidance to and from choice points.” Curr Opin Neurobiol 8(1):64-72 Details Keynes R (1998), “Evanescent science” Curr Biol 8(1):R4 Details Tannahill D, Cook GMW, Keynes RJ (1998), “Axon guidance and somites” Cell Tissue Res 291(2):363 Details 1997Tannahill D, Cook GM, Keynes RJ (1997), “Axon guidance and somites.” Cell Tissue Res 290(2):275-83 Details 1996Keynes R, Cook GM (1996), “Axons turn as netrins find their receptor.” Neuron 17(6):1031-4 Details 1995Fok-Seang J, Smith-Thomas LC, Meiners S, Muir E, Du JS, Housden E, Johnson AR, Faissner A, Geller HM, Keynes RJ (1995), “An analysis of astrocytic cell lines with different abilities to promote axon growth.” Brain Res 689(2):207-23 Details Keynes R, Cook GM (1995), “Axon guidance molecules.” Cell 83(2):161-9 Details Keynes RJ, Cook GM (1995), “Repulsive and inhibitory signals.” Curr Opin Neurobiol 5(1):75-82 Details Larner AJ, Johnson AR, Keynes RJ (1995), “Regeneration in the vertebrate central nervous system: phylogeny, ontogeny, and mechanisms.” Biol Rev Camb Philos Soc 70(4):597-619 Details 1994Keynes R, Krumlauf R (1994), “Hox genes and regionalization of the nervous system.” Annu Rev Neurosci 17:109-32 Details Lumsden A, Clarke JD, Keynes R, Fraser S (1994), “Early phenotypic choices by neuronal precursors, revealed by clonal analysis of the chick embryo hindbrain.” Development 120(6):1581-9 Details 1992Keynes RJ, Cook GM (1992), “Contact inhibition of growth-cone motility during peripheral nerve segmentation.” Biochem Soc Trans 20(2):399-401 Details Keynes RJ, Cook GM (1992), “Repellent cues in axon guidance.” Curr Opin Neurobiol 2(1):55-9 Details McClure MO, Moore JP, Blanc DF, Scotting P, Cook GM, Keynes RJ, Weber JN, Davies D, Weiss RA (1992), “Investigations into the mechanism by which sulfated polysaccharides inhibit HIV infection in vitro.” AIDS Res Hum Retroviruses 8(1):19-26 Details 1991Feneley MR, Fawcett JW, Keynes RJ (1991), “The role of Schwann cells in the regeneration of peripheral nerve axons through muscle basal lamina grafts.” Exp Neurol 114(3):275-85 Details Keynes RJ, Jaques KF, Cook GM (1991), “Axon repulsion during peripheral nerve segmentation.” Development Suppl 2:131-9 Details Keynes RJ, Johnson AR, Picart CJ, Dunin-Borkowski OM, Cook GM (1991), “A growth cone collapsing activity in chicken gray matter.” Ann N Y Acad Sci 633:562 Details Lim TM, Jaques KF, Stern CD, Keynes RJ (1991), “An evaluation of myelomeres and segmentation of the chick embryo spinal cord.” Development 113(1):227-38 Details Stern CD, Jaques KF, Lim TM, Fraser SE, Keynes RJ (1991), “Segmental lineage restrictions in the chick embryo spinal cord depend on the adjacent somites.” Development 113(1):239-44 Details 1990Fawcett JW, Keynes RJ (1990), “Peripheral nerve regeneration.” Annu Rev Neurosci 13:43-60 Details Greenberg JM, Boehm T, Sofroniew MV, Keynes RJ, Barton SC, Norris ML, Surani MA, Spillantini MG, Rabbits TH (1990), “Segmental and developmental regulation of a presumptive T-cell oncogene in the central nervous system.” Nature 344(6262):158-60 Details Keynes R, Cook G, Davies J, Lumsden A, Norris W, Stern C (1990), “Segmentation and the development of the vertebrate nervous system.” J Physiol (Paris) 84(1):27-32 Details Keynes R, Lumsden A (1990), “Segmentation and the origin of regional diversity in the vertebrate central nervous system.” Neuron 4(1):1-9 Details Scotting PJ, Hewitt M, Keynes RJ (1990), “Isolation and analysis of chick homeobox cDNA clones.” Nucleic Acids Res 18(13):3999 Details 1989Norris WE, Stern CD, Keynes RJ (1989), “Molecular differences between the rostral and caudal halves of the sclerotome in the chick embryo.” Development 105(3):541-8 Details Primmett DR, Norris WE, Carlson GJ, Keynes RJ, Stern CD (1989), “Periodic segmental anomalies induced by heat shock in the chick embryo are associated with the cell cycle.” Development 105(1):119-30 Details Stern CD, Norris WE, Bronner-Fraser M, Carlson GJ, Faissner A, Keynes RJ, Schachner M (1989), “J1/tenascin-related molecules are not responsible for the segmented pattern of neural crest cells or motor axons in the chick embryo.” Development 107(2):309-19 Details 1988Keynes RJ, Stern CD (1988), “Mechanisms of vertebrate segmentation.” Development 103(3):413-29 Details Primmett DR, Stern CD, Keynes RJ (1988), “Heat shock causes repeated segmental anomalies in the chick embryo.” Development 104(2):331-9 Details Stern CD, Fraser SE, Keynes RJ, Primmett DR (1988), “A cell lineage analysis of segmentation in the chick embryo.” Development 104 Suppl:231-44 Details Stern CD, Keynes RJ (1988), “Spatial patterns of homeobox gene expression in the developing mammalian CNS.” Trends Neurosci 11(5):190-2 Details 1987Keynes RJ, Stirling RV, Stern CD, Summerbell D (1987), “The specificity of motor innervation of the chick wing does not depend upon the segmental origin of muscles.” Development 99(4):565-75 Details Lim TM, Lunn ER, Keynes RJ, Stern CD (1987), “The differing effects of occipital and trunk somites on neural development in the chick embryo.” Development 100(3):525-33 Details Lunn ER, Scourfield J, Keynes RJ, Stern CD (1987), “The neural tube origin of ventral root sheath cells in the chick embryo.” Development 101(2):247-54 Details 1986Fawcett JW, Keynes RJ (1986), “Muscle basal lamina: a new graft material for peripheral nerve repair.” J Neurosurg 65(3):354-63 Details 1985Hopkins WG, Brown MC, Keynes RJ (1985), “Postnatal growth of motor nerve terminals in muscles of the mouse.” J Neurocytol 14(4):525-40 Details 1984Booth CM, Brown MC, Keynes RJ, Barclay AN (1984), “Muscles of adult rats and mice express the Thy-1 glycoprotein on denervation.” Brain Res 308(2):380-2 Details Keynes RJ, Hopkins WG, Huang LH (1984), “Regeneration of mouse peripheral nerves in degenerating skeletal muscle: guidance by residual muscle fibre basement membrane.” Brain Res 295(2):275-81 Details Robb GA, Keynes RJ (1984), “Stimulation of nodal and terminal sprouting of mouse motor nerves by gangliosides.” Brain Res 295(2):368-71 Details 1983Huang CL, Keynes RJ (1983), “Terminal sprouting of mouse motor nerves when the post-synaptic membrane degenerates.” Brain Res 274(2):225-9 Details Keynes RJ, Hopkins WG, Brown MC (1983), “Sprouting of mammalian motor neurones at nodes of Ranvier: the role of the denervated motor endplate.” Brain Res 264(2):209-13 Details 1982Brown MC, Hopkins WG, Keynes RJ (1982), “Short- and long-term effects of paralysis on the motor innervation of two different neonatal mouse muscles.” J Physiol 329:439-50 Details Brown MC, Hopkins WG, Keynes RJ (1982), “Importance of pathway formation for nodal sprout production in partly denervated muscles.” Brain Res 243(2):345-9 Details Brown MC, Hopkins WG, Keynes RJ (1982), “Comparison of effects of denervation and botulinum toxin paralysis on muscle properties in mice.” J Physiol 327:29-37 Details Brown MC, Hopkins WG, Keynes RJ, White I (1982), “A comparison of early morphological changes at denervated and paralyzed endplates in fast and slow muscles of the mouse.” Brain Res 248(2):382-6 Details Keynes RJ (1982), “The effects of pyronin on sprouting and regeneration of mouse motor nerves.” Brain Res 253(1-2):13-8 Details Keynes RJ, Smith GW, Slater JD, Brown MM, Brown SE, Payne NN, Jowett TP, Monge CC (1982), “Renin and aldosterone at high altitude in man.” J Endocrinol 92(1):131-40 Details Warren JB, Keynes RJ, Brown MJ, Jenner DA, McNicol MW (1982), “Blunted sympathoadrenal response to exercise in asthmatic subjects.” Br J Dis Chest 76(2):147-50 Details 1981Brown MC, Holland RL, Hopkins WG, Keynes RJ (1981), “An assessment of the spread of the signal for terminal sprouting within and between muscles.” Brain Res 210(1-2):145-51 Details Hopkins WG, Brown MC, Keynes RJ (1981), “Nerve growth from nodes of Ranvier in inactive muscle.” Brain Res 222(1):125-8 Details |