CHRONOTOPIC FIBER REORDERING AND THE DISTRIBUTION OF CELL-ADHESION AND EXTRACELLULAR-MATRIX MOLECULES IN THE OPTIC PATHWAY OF FETAL FERRETS

We have examined the age-related reordering of optic axons as they pas s through the chiasmatic region in fetal ferrets. Proportions of young and old optic axons were determined from electron micrographs taken s equentially through the prechiasmatic nerve, chasm, and tract. This '' chronotopic'' reordering of axons was shown to emerge gradually, begin ning rostral to the fusion of the two optic nerves, but continuing to develop caudal to the chiasmatic midline. Segregation of young from ol d optic axons was most pronounced within the optic tract. We then comp ared the emergence of this fiber reorganization to the distribution of cell adhesion and extracellular matrix molecules and to the glial arc hitecture within the pathway. Using immunohistochemistry, the distribu tions of the cell adhesion molecules L1, NCAM, and TAG-1 and the extra cellular matrix molecules laminin-l and chondroitin sulfate proteoglyc ans (CSPGs) were determined. Among these, only the distribution of CSP Gs was observed to change in a manner that complemented the segregatio n of young from old optic axons. CSPGs were densest in the deeper part s of the optic tract, coincident with radial glial fibers that turn to course within the region of the oldest optic axons. Both the glial ar chitecture and the CSPG distribution form as a consequence of the inva sion of the first optic axons, shown by the developmental sequence of each, and by the fact that these glial and molecular features fail to form in the absence of optic axons. The data suggest a model in which the gradient of CSPGs across the depth of the tract contributes to the formation of the chronotopic fiber reordering by providing a relative ly unfavorable environment for subsequent axonal growth. The CSPGs may do so by interfering with adhesion molecules on optic axons that norm ally promote elongation. (C) 1997 Wiley-Liss, Inc.