Neural Influence on the Extracellular Matrix During Blastema Formation

Summary

By investigating reinnervation of denervated/amputated limbs of urodele (Ambystoma mexicanum) larvae, it is shown that nerves affect hyaluronate accumulation in the extracellular matrix as well as mitotic activity in cells of distal, dedifferentiated regions of the limb stump. Accumulation of hyaluronate is increased two-fold and mitotic activity is stimulated four-fold over that seen immediately prior to the reappearance of nerve fibers in the distal areas. Formation of a hyaluronate-rich matrix is accompanied by enlargement of the intercellular space and a decrease in cell density, which occur simultaneously with the appearance of a morphologically recognizable blastema on the tip of the limb stump. The increase in proliferative activity includes cells which entered the cell cycle in response to the amputation injury and incorporated ³H-thymidine five days later. These results indicate that nerves promote blastema formation and growth both by stimulation cell division and by enhancing production of a large extracellular component important for expansion of intercellular space and tissue volume. Work by others with cultured mesenchymal cells and purified growth factors suggests that such factors stimulate both cell cycling and hyaluronate production as part of a single mitogenic effect.