A Dual Role oferbB2in Myelination and in Expansion of the Schwann Cell Precursor Pool

2000/03/06 by Alistair N. Garratt, Octavian Voiculescu, Piotr Topilko +2 · 26 citations
Neuroscience · #Axon Guidance and Neuronal Signaling #Hereditary Neurological Disorders #Nerve injury and regeneration

paper · pdf · doi:10.1083/jcb.148.5.1035

Abstract

Neuregulin-1 provides an important axonally derived signal for the survival and growth of developing Schwann cells, which is transmitted by the ErbB2/ErbB3 receptor tyrosine kinases. Null mutations of the neuregulin-1, erbB2, or erbB3 mouse genes cause severe deficits in early Schwann cell development. Here, we employ Cre-loxP technology to introduce erbB2 mutations late in Schwann cell development, using a Krox20-cre allele. Cre-mediated erbB2 ablation occurs perinatally in peripheral nerves, but already at E11 within spinal roots. The mutant mice exhibit a widespread peripheral neuropathy characterized by abnormally thin myelin sheaths, containing fewer myelin wraps. In addition, in spinal roots the Schwann cell precursor pool is not correctly established. Thus, the Neuregulin signaling system functions during multiple stages of Schwann cell development and is essential for correct myelination. The thickness of the myelin sheath is determined by the axon diameter, and we suggest that trophic signals provided by the nerve determine the number of times a Schwann cell wraps an axon.

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• Efficient isolation and gene expression profiling of small numbers of neural crest stem cells and developing Schwann cells. [europepmc]
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• Mechanisms and roles of axon-Schwann cell interactions. [europepmc]
• Neuregulin-1 type III determines the ensheathment fate of axons. [europepmc]
• ErbB2 signaling in Schwann cells is mostly dispensable for maintenance of myelinated peripheral nerves and proliferation of adult Schwann cells after injury. [europepmc]
• Neuregulin 1-erbB signaling is necessary for normal myelination and sensory function. [europepmc]
• Skin-derived precursors generate myelinating Schwann cells for the injured and dysmyelinated nervous system. [europepmc]
• Induction of neuregulin signaling in mouse schwann cells in vivo mimics responses to denervation. [europepmc]
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• Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system. [europepmc]
• A G protein-coupled receptor is essential for Schwann cells to initiate myelination. [europepmc]
• Nrg1/ErbB signaling networks in Schwann cell development and myelination. [europepmc]
• Oligodendrocyte PTEN is required for myelin and axonal integrity, not remyelination. [europepmc]
• Yy1 as a molecular link between neuregulin and transcriptional modulation of peripheral myelination. [europepmc]
• Specific functions for ERK/MAPK signaling during PNS development. [europepmc]
• Wallerian degeneration: the innate-immune response to traumatic nerve injury. [europepmc]
• The role of neuregulin-1 in the response to nerve injury. [europepmc]
• Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. [europepmc]
• Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases. [europepmc]
• How Schwann Cells Sort Axons: New Concepts. [europepmc]
• New insights on Schwann cell development. [europepmc]
• YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells. [europepmc]
• Schwann Cell Precursors; Multipotent Glial Cells in Embryonic Nerves. [europepmc]
• Role of EGFR in the Nervous System. [europepmc]

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