DOMAIN-SPECIFIC ANTIBODIES AGAINST THE B2 CHAIN OF LAMININ INHIBIT NEURONAL MIGRATION IN THE NEONATAL RAT CEREBELLUM

Although the spatial and temporal patterns of neuronal migration have been analyzed in great detail, little direct evidence is available as to what extracellular matrix molecules are involved. Because there is indirect evidence implicating the extracellular matrix protein laminin in neuronal migration, we investigated the effects of antibodies agai nst a synthetic peptide derived from a neurite outgrowth domain of the B2 chain of laminin on neuronal migration in living cerebellar slices . We show by using infrared video microscopy that divalent Fab(2) frag ments of these antibodies inhibit granule neuronal movement in living slices of (P8) rat cerebellum. This inhibition of neuronal movement ma nifests itself by cessation of both radial and horizontal translocatio ns of nuclei inside the granule neuronal processes. Fab(2) fragments o f antibodies against the intact (native) laminin molecule or Fab(2) fr agments from the preimmune serum do not affect nuclear translocation. Immunocytochemistry shows binding of the divalent Fab(2) fragments of the B2 chain-specific antibodies to the Purkinje and Bergmann glial ce ll areas, and as punctate deposits in between the cells of the externa l granule cell layer. Native laminin antibodies bind to the basement m embranes, and binding of the Fab, fragments from the preimmune sera ca nnot be demonstrated. These results indicate that neuronal migration i n the postnatal rat cerebellum in vivo involves nuclear translocation that can be inhibited by antibodies against a neurite outgrowth domain of the B2 chain of laminin. Thus, migration of cerebellar granule neu rons may depend on the interaction between a neurite outgrowth domain of the B2 chain of laminin and neuronal cytoskeleton involved in nucle ar movement. (C) 1995 Wiley-Liss, Inc.