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Axonal growth towards Xenopus skin in vitro is mediated by matrix metalloproteinase activity |
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| Authors: | David Tonge Ning Zhu Steven Lynham Pascal Leclere Alison Snape Alison Brewer Uwe Schlomann Taheera Ferdous Charlene Tennyson Jörg W. Bartsch Malcolm Ward John Pizzey |
| Affiliation: | 1. Wolfson Centre for Age‐Related Diseases, King's College London, , London Bridge, London, SE1 1UL UK;2. Centre of Excellence for Mass Spectrometry, Institute of Psychiatry, King's College London, , UK;3. School of Medicine, King's College London, , UK;4. Cardiovascular Division, King's College London, , UK;5. Pharmaceutical Science Research Division, King's College London, , UK;6. Proteome Sciences plc, Institute of Psychiatry, King's College London, , UK |
| Abstract: | We have previously demonstrated that the growth of peripheral nervous system axons is strongly attracted towards limb buds and skin explants in vitro. Here, we show that directed axonal growth towards skin explants of Xenopus laevis in matrigel is associated with expression of matrix metalloproteinase (MMP)‐18 and also other MMPs, and that this long‐range neurotropic activity is inhibited by the broad‐spectrum MMP inhibitors BB‐94 and GM6001. We also show that forced expression of MMP‐18 in COS‐7 cell aggregates enhances axonal growth from Xenopus dorsal root ganglia explants. Nidogen is the target of MMPs released by cultured skin in matrigel, whereas other components remain intact. Our results suggest a novel link between MMP activity and extracellular matrix breakdown in the control of axonal growth. |
| Keywords: | axon guidance cultured neurons extracellular matrix neurotrophin proteomics |