Factors affecting schwann cell basal lamina formation in cultures of dorsal root ganglia from mice with muscular dystrophy.

Pure populations of sensory neurons (N), Schwann cells (S) and fibroblasts (Fb) were established in culture from normal and dystrophic (dy) mice in order to investigate the cellular origin(s) of the peripheral nervous system abnormalities present in murine muscular dystrophy. These cell types were placed together in various combinations and their subsequent interactions were monitored with the light and electron microscope. The formation of the basal lamina (BL) which in normal tissue, completely surrounds the external aspect of the Schwann cell (when in contact with axons) was documented by morphometric analysis of electron micrographs. Defects in Schwann cell BL formation, observed throughout the PNS of the dy mouse in vivo, were used as a marker for the expression of the dystrophic abnormality in culture. Initially mature cultures of dy tissues containing only S and N (SN) without Fb were examined and found to contain an incomplete BL that surrounded only 82.8 +/- 12.2% of the externally directed plasmalemma of axon-related Schwann cells. The following recombination cultures were established: (1) normal S were placed on dystrophic N; (2) dystrophic S were placed on dystrophic N; (3) dystrophic S were placed on normal N; and (4) normal Fb were added to a dystrophic SN culture. After a 5-week period, the BL formed by normal S in direct contact with dystrophic N was thick and continuous (97.7 +/- 2.2 coverage). On the other hand, in culture situations (without Fb) containing dystrophic S in contact with either dystrophic or normal neurites, the BL coverage was considerably less (58.5 +/- 14.8% and 55.4 +/- 13.2%, respectively). The addition of normal Fb obtained from sciatic nerve explants to dystrophic SN cultures in time resulted in the formation of a morphologically complete BL (98.9 +/- 1.4% coverage). We conclude that neuronal signal(s) are adequate to induce complete BL formation by Schwann cells in the dystrophic tissue but that dystrophic Schwann cells are incapable of forming a complete BL. Furthermore, this deficiency of dy Schwann cells is apparently corrected by the presence of normal Fb by an unknown mechanism.