How do myelinated axons signal to the nuclei of cells that enwrap them? The cell bodies of oligodendrocytes and Schwann cells are segregated from axons by multiple layers of bimolecular lipid leaflet and myelin proteins. Conventional signal transduction strategies would seem inadequate to the challenge without special adaptations. Wallerian degeneration provides a model to study axon-to-Schwann...

We investigated (a) if activation of the mitogen activated protein kinase (MAPK) pathway was linked to the stress activated protein kinase (SAPK) pathway and (b) if JNK was required for activation of c-Jun in Schwann cells of rat sciatic nerve following injury. To this aim, ERK1/2 and the transcription factors c-Jun and ATF-3 were studied by immunohistochemistry in segments of transected nerves...

During postnatal development in the peripheral nerve, differentiating Schwann cells are susceptible to apoptotic death. Schwann cell apoptosis is regulated by axons and serves as one mechanism through which axon and Schwann cell numbers are correctly matched. This regulation is mediated in part by the provision of limiting axon-derived trophic molecules, although neuregulin-1 (NRG-1) is the onl...

In development of the peripheral nervous system, Schwann cells proliferate, migrate, and ultimately differentiate to form myelin sheath. In all of the myelination stages, Schwann cells continuously undergo morphological changes; however, little is known about their underlying molecular mechanisms. We previously cloned the dock7 gene encoding the atypical Rho family guanine-nucleotide exchange f...

Multiple discontinuities are observed in the basal laminas of Schwann cells in mature dystrophic mice. To explore the pathogenesis of this abnormality we have exploited a dystrophic in equilibrium shiverer mouse chimera preparation in which both the basal lamina phenotype and the genotype of myelin-forming Schwann cells can be determined. If the basal lamina abnormality were to arise from an in...

We show that highly pure populations of human Schwann cells can be derived rapidly and in a straightforward way, without the need for genetic manipulation, from human epidermal neural crest stem cells [hEPI-NCSC(s)] present in the bulge of hair follicles. These human Schwann cells promise to be a useful tool for cell-based therapies, disease modelling and drug discovery. Schwann cells are glia ...

Dystroglycan is a central component of the dystrophin-glycoprotein complex (DGC) that links extracellular matrix with cytoskeleton, expressed in a variety of fetal and adult tissues. Dystroglycan plays diverse roles in development and homeostasis including basement membrane formation, epithelial morphogenesis, membrane stability, cell polarization, and cell migration. In this paper, we will foc...

Schwann cell dedifferentiation from a myelinating to a progenitor-like cell underlies the remarkable ability of peripheral nerves to regenerate following injury. However, the molecular identity of the differentiated and dedifferentiated states in vivo has been elusive. Here, we profiled Schwann cells acutely purified from intact nerves and from the wound and distal regions of severed nerves. Ou...

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF) beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGFbeta receptor is specif...

We have studied the transcription factors SCIP and Krox-20 in differentiating Schwann cells-during normal development, in experimentally induced degenerating and regenerating peripheral nerves, and in cell culture-and have compared the expression of these regulators to a battery of genes that mark distinct stages in Schwann cell differentiation. In the myelinating Schwann cell lineage, we find ...