Although mutations in multiple genes are associated with inherited demyelinating neuropathies, the molecular components and pathways crucial for myelination remain largely unknown. To approach this question, we performed genome-wide expression analysis in several paradigms where the status of peripheral nerve myelination is dynamically changing. Anchor gene correlation analysis, a form of micro...

Salla disease and infantile sialic acid storage disease are autosomal recessive lysosomal storage disorders caused by mutations in the gene encoding sialin, a membrane protein that transports free sialic acid out of the lysosome after it is cleaved from sialoglycoconjugates undergoing degradation. Accumulation of sialic acid in lysosomes defines these disorders, and the clinical phenotype is ch...

In developing peripheral nerves, differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years, there has been an increased understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination, together with a growing appreciation of some of the signaling pathways involved. H...

During peripheral nervous system development, Schwann cells (SCs) surrounding single large axons differentiate into myelinating SCs. Previous studies implicate RhoGTPases in SC myelination, but the mechanisms involved in RhoGTPase regulation of SC myelination are unknown. Here, we show that SC myelination is arrested in Rac1 conditional knock-out (Rac1-CKO) mice. Rac1 knock-out abrogated phosph...

The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits Schwann cell (SC) migration and promotes myelination via the p75 neurotrophin receptor (NTR). Despite these recent findings, the expression, localization, and mechanism of BDNF action has yet to be determined. Here we demonstrate that the sensory neurons of the dorsal root ganglion (DRG) are a major source of BDNF during postnat...

The formation of the myelin sheath is a crucial step during development because it enables fast and efficient propagation of signals within the limited space of the mammalian central nervous system (CNS). During the process of myelination, oligodendrocytes actively interact with the extracellular matrix (ECM). These interactions are considered crucial for proper and timely completion of the mye...

Morphological, autoradiographic, and biochemical methods were used to study the time of appearance, distribution, and nature of sulfated constituents in the developing rat optic nerve. Electron microscope studies showed that myelination begins (6 days postnatal) shortly after the appearance of oligodendroglia (5 days postnatal). Over the ensuing 3 wk, myelination increased rapidly. During the 1...

PURPOSE To investigate the use of a three-pool relaxation model to measure myelin, myelinated-axon, and mixed water-pool fractions in white matter (WM) during myelination. MATERIALS AND METHODS MRI at 1.9 Tesla, and conventional spin-echo imaging were used to acquire T1 and T2 relaxation data in 15 normal children ranging in age from 3 months to 13 years 4 months. Three equations with three u...

Myelination depends on the synthesis of large amounts of myelin transcripts and proteins and is controlled by Nrg1/ErbB/Shp2 signaling. We developed a novel pulse labeling strategy based on stable isotope labeling with amino acids in cell culture (SILAC) to measure the dynamics of myelin protein production in mice. We found that protein synthesis is dampened in the maturing postnatal peripheral...

Oligodendrocyte differentiation and myelination are tightly regulated processes orchestrated by a complex transcriptional network. Two bHLH transcription factors in this network, Olig1 and Olig2, are expressed exclusively by oligodendrocytes after late embryonic development. Although the role of Olig2 in the lineage is well established, the role of Olig1 is still unclear. The current studies an...