title: Axonal growth towards Xenopus skin in vitro is mediated by matrix metalloproteinase activity.
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.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK.
authors.forename: David
authors.initials: D
authors.lastname: Tonge
authors.forename: Ning
authors.initials: N
authors.lastname: Zhu
authors.forename: Steven
authors.initials: S
authors.lastname: Lynham
authors.forename: Pascal
authors.initials: P
authors.lastname: Leclere
authors.forename: Alison
authors.initials: A
authors.lastname: Snape
authors.forename: Alison
authors.initials: A
authors.lastname: Brewer
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlomann
authors.forename: Taheera
authors.initials: T
authors.lastname: Ferdous
authors.forename: Charlene
authors.initials: C
authors.lastname: Tennyson
authors.forename: Jörg W
authors.initials: JW
authors.lastname: Bartsch
authors.forename: Malcolm
authors.initials: M
authors.lastname: Ward
authors.forename: John
authors.initials: J
authors.lastname: Pizzey
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D055495:Neurogenesis / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000294:innervation*; D014981:Xenopus
chemical_list: D012333:RNA, Messenger; D020782:Matrix Metalloproteinases