A developmentally regulated switch directs regenerative growth of Schwann cells through cyclin D1

Sciatic nerve axons in cyclin D1 knockout mice develop normally, become pro perly ensheathed by Schwann cells, and appear to function normally. However , in the Wallerian degeneration model of nerve injury, the mitotic response of Schwann cells is completely inhibited. The mitotic block is Schwann cel l autonomous and developmentally regulated. Rescue analysis (by "knockin" o f cyclin E) indicates that D1 protein, rather than regulatory elements of t he D1 gene, provides the essential Schwann cell function. Genetic inhibitio n of the Schwann cell cycle shows that neuronal responses to nerve injury a re surprisingly independent of Schwann cell mitotic responses. Even axonal regrowth into the distal zone of a nerve crush injury is not markedly impai red in cyclin D1(-/-) mice.