Urokinase-type plasminogen activator (uPA) promotes the cell migration and the axonal outgrowth in the developing optic lobe

DI MARTINO C.; DAQUARTI G.; BARBER M.; LOPEZ COSTA J.J.; FLOES V. AND SANCHEZ V

San Diego, EE.UU

Congreso; 37th Annual Meeting of the Society of Neuroscience.; 2007

Society for Neuroscience

Cell migration and neuritogenesis are the result of a complex balance between localized proteolysis, cell-extracellular matrix interactions and cytoskeletal reorganization. The complex urokinase-type plasminogen activator/ urokinase-type plasminogen activator receptor (uPA-uPAR) appears to participate as a component in the coordination of these events. It is known that in fibroblasts and neutrophils the binding of uPA to uPAR induces activation of specific signaling molecules such as FAK, MAPK and the Jack/Stat pathway. The chick optic tectum (OT) shows a multilaminar cortical architecture composed of alternating neuronal and fibrous layers. This structure is the result of an ordered process of neuronal migration during the embryonic development. The aim of this work is to investigate the rol of uPA in the processes of cell migration and neuritogenesis using the OT as biological model. OT from embryos of 6 days were dissected and separated in cephalic and caudal portions. Explants of each portion were grown for 20 hs in DMEM supplemented with glutamine and N2, with or without uPA in a final concentration of 200 mUI/ml to investigate if it induces neurite outgrowth and cell migration; or plasminogen activator inhibitor-1 (PAI-1) in a final concentration of 20 mUI/ml in order to know if the inhibitor of endogenous uPA alter the axonal growth or the migration processes. After this time the explants were observed by phase-contrast microscopy and photographed. We measured two different variables (a) the cell migration pattern and (b) the axonal length. The cell migration process was estimated by the distance from the border of explants to the migrating cell bodies. The results show that the axonal length in caudal portions is larger than the cephalic ones in control explants (26%, p