Control of nerve fiber growth in culture by components of the extracellular matrix

What are the guiding forces within the normally developing brain that control the far ranging growth routes of "pioneer" axons? We have examined this question in two systems (the optic chiasm and corpus callosum of embryonic mice) and in places along each of these pathways where very large populations of early growing fibers make a drastic change in direction, en masse, while on route to their targets. In both systems, we have found a variety of transiently forming bridgeor barricade-like glial structures located at these critical points. Such glial formations are absent in mutant (acallosal) embryos where the outgrowing fibers become lost. Furthermore, we have recently been successful in restoring the malformed corpus eallosum in postnatal acallosal mice by providing the misplaced axons with a glial prosthesis that closely resembles (in both cell type and orientation) the environment that the axons would have encountered in the normally developing embryo. The results suggest that local environmental factors and~ in particular, glial cells (a special population of presumptive astrocytes) are extremely important in guiding axons during normal and regenerative development in the mammalian central nervous system.