KROX-20 CONTROLS MYELINATION IN THE PERIPHERAL NERVOUS-SYSTEM

THE molecular mechanisms controlling the process of myelination by Sch wann cells remain elusive, despite recent progress in the identificati on and characterization of genes encoding myelin components (reviewed in ref. 1). We have created a null allele in the mouse Krox-20 gene, w hich encodes a zinc-finger transcription factor(2,3), by in-frame inse rtion of the Escherichia coli lacZ gene, and have shown that hindbrain segmentation is affected in Krox-20(-/-) embryos(4). We demonstrate h ere that Krox-20 is also activated in Schwann cells before the onset o f myelination and that its disruption blocks Schwann cells at an early stage in their differentiation, thus preventing myelination in the pe ripheral nervous system. In Krox-20(-/-) mice, Schwann cells wrap thei r cytoplasmic processes only one and a half turns around the axon, and although they express the early myelin marker, myelin-associated glyc oprotein(5), late myelin gene products are absent, including those for protein zero(6) and myelin basic protein(7). Therefore Krox-20 is lik ely to control a set of genes required for completion of myelination i n the peripheral nervous system.