Chilton, John - University of Exeter

个人简介

M.A.(Hons.) Natural Sciences M.Sc. Neuroscience D.Phil. Developmental neurobiology Postgraduate Certificate in Clinical Education Fellow of the Higher Education Academy

研究领域

His work focuses on a class of proteins called semaphorins which can both inhibit and promote neuronal growth. In collaboration with Prof. Sarah Guthrie at King’s College London, he has shown that strabismus (squint) results from defective semaphorin signalling causing miswiring of the oculomotor system that controls eye movements. To exert their action, semaphorins bind to extracellular receptors which send signals to modulate the neuronal cytoskeleton, an intracellular scaffold responsible for cell shape, growth and motility. We have demonstrated that a protein called drebrin which regulates the actin component of the cytoskeleton is necessary for neuronal migration and morphology. The research group believes that drebrin may be a crucial link between semaphorin signalling and the actin network. Levels of drebrin are reduced in Alzheimer Disease and Down Syndrome so our work is also relevant to the regeneration of circuits later in life by reactivating developmental mechanisms. The oculomotor system is among the few motor nerves that are relatively spared in motor neuron diseases. Uncovering the reasons behind this resistance to degeneration could open new avenues to restore function. Calcium ions are a key intracellular messenger in neurons but must be tightly regulated to avoid overloading and ultimately killing nerve cells. The group has begun to study the role of a class of proteins called neuronal calcium sensors which may form part of the protective mechanism. Dr Chilton gives an overview of this research in the video below, filmed at the Living Systems Institute Symposium in March 2016.

近期论文

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Ketschek A, Spillane M, Dun X-P, Hardy H, Chilton J, Gallo G (2016). Drebrin coordinates the actin and microtubule cytoskeleton during the initiation of axon collateral branches. Developmental Neurobiology, 76(10), 1092-1110. Full text. Gutowski NJ, Chilton JK (2015). The congenital cranial dysinnervation disorders. Archives of Disease in Childhood, 100(7), 678-681. Abstract. Article has an altmetric score of 4 Gutowski NJ, Chilton JK (2015). The congenital cranial dysinnervation disorders. Arch Dis Child, 100(7), 678-681. Abstract. Author URL. Article has an altmetric score of 4 Chilton JK, Ferrario JE, Baskaran P, Clark C, Hendry A, Lerner O, Hintze M, Guthrie S (2013). Axon guidance in the developing ocular motor system and Duane's Retration Syndrome depends on Semaphorin signalling via alpha2-chimaerin. PNAS Article has an altmetric score of 1 Dun XP, Bandeira de Lima T, Allen J, Geraldo S, Gordon-Weeks P, Chilton JK (2012). Drebrin controls neuronal migration through the formation and alignment of the leading process. Mol Cell Neurosci, 49(3), 341-350. Abstract. Author URL. Full text. Ketschek A, Spillane M, Dun X-P, Chilton J, Gallo G (2012). Regulation of axonal filopodia and collateral branches by the actin filament binding protein drebrin. MOLECULAR BIOLOGY OF THE CELL, 23 Author URL. Dun XP, Chilton JK (2010). Control of cell shape and plasticity during development and disease by the actin-binding protein Drebrin. Histol Histopathol, 25(4), 533-540. Abstract. Author URL. Allen J, Chilton JK (2009). The specific targeting of guidance receptors within neurons: who directs the directors?. Dev Biol, 327(1), 4-11. Abstract. Author URL. Miyake N, Chilton J, Psatha M, Cheng L, Andrews C, Chan WM, Law K, Crosier M, Lindsay S, Cheung M, et al (2008). Human CHN1 mutations hyperactivate alpha2-chimaerin and cause Duane's retraction syndrome. Science, 321(5890), 839-843. Abstract. Author URL. Article has an altmetric score of 12 Geraldo S, Khanzada UK, Parsons M, Chilton JK, Gordon-Weeks PR (2008). Targeting of the F-actin-binding protein drebrin by the microtubule plus-tip protein EB3 is required for neuritogenesis. Nat Cell Biol, 10(10), 1181-1189. Abstract. Author URL. Lee S, Faux C, Nixon J, Alete D, Chilton J, Hawadle M, Stoker AW (2007). Dimerization of protein tyrosine phosphatase sigma governs both ligand binding and isoform specificity. Mol Cell Biol, 27(5), 1795-1808. Abstract. Author URL. Article has an altmetric score of 1 Chilton J (2006). Molecular mechanisms of axon guidance. Developmental Biology, 292(1), 13-24. Article has an altmetric score of 1 Chilton J, Faure J, Peris L, Thery M (2006). Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends. The Journal of Cell Biology, 174(6), 839-849. Osborne NJ, Begbie J, Chilton JK, Schmidt H, Eickholt BJ (2005). Semaphorin/neuropilin signaling influences the positioning of migratory neural crest cells within the hindbrain region of the chick. Dev Dyn, 232(4), 939-949. Abstract. Author URL. Chilton J, Hammond R, Naeem A, Vivancos V (2005). Slit-mediated repulsion is a key regulator of motor axon pathfinding in the hindbrain. Development, 132(20), 4483-4495. Article has an altmetric score of 4 Chilton J, Guthrie S (2004). Development of the oculomotor axon projections in the chick embryo. The Journal of Comparative Neurology, 472(3), 308-317. Chilton JK, Guthrie S (2003). Cranial expression of class 3 secreted semaphorins and their neuropilin receptors. Dev Dyn, 228(4), 726-733. Abstract. Author URL. Sajnani-Perez G, Chilton JK, Aricescu AR, Haj F, Stoker AW (2003). Isoform-specific binding of the tyrosine phosphatase PTPsigma to a ligand in developing muscle. Mol Cell Neurosci, 22(1), 37-48. Abstract. Author URL. Chilton JK, Stoker AW (2000). Expression of receptor protein tyrosine phosphatases in embryonic chick spinal cord. Mol Cell Neurosci, 16(4), 470-480. Abstract. Author URL. Chilton JK, Stoker AW (2000). Spatiotemporal distribution of the ligands for both isoforms of the protein tyrosine phosphatase crypalpha in embryonic chick spinal cord and limbs. EUROPEAN JOURNAL OF NEUROSCIENCE, 12, 266-266. Author URL.