Learn More
Conditional mutagenesis permits the cell type-specific analysis of gene functions in vivo. Here, we describe a mouse line that expresses Cre recombinase under control of regulatory sequences of NEX, a gene that encodes a neuronal basic helix-loop-helix (bHLH) protein. To mimic endogenous NEX expression in the dorsal telencephalon, the Cre recombinase gene(More)
In the nervous system of vertebrates, myelination is essential for rapid and accurate impulse conduction. Myelin thickness depends on axon fiber size. We use mutant and transgenic mouse lines to show that axonal Neuregulin-1 (Nrg1) signals information about axon size to Schwann cells. Reduced Nrg1 expression causes hypomyelination and reduced nerve(More)
Signal transduction pathways are modular composites of functionally interdependent sets of proteins that act in a coordinated fashion to transform environmental information into a phenotypic response. The pro-inflammatory cytokine tumour necrosis factor (TNF)-α triggers a signalling cascade, converging on the activation of the transcription factor NF-κB,(More)
After peripheral nerve injury, axons regenerate and become remyelinated by resident Schwann cells. However, myelin repair never results in the original myelin thickness, suggesting insufficient stimulation by neuronal growth factors. Upon testing this hypothesis, we found that axonal neuregulin-1 (NRG1) type III and, unexpectedly, also NRG1 type I restored(More)
Neuregulin 1 (NRG1) is a pleiotropic growth factor involved in diverse aspects of brain development and function. In schizophrenia, expression of the NRG1 type I isoform is selectively increased. However, virtually nothing is known about the roles of this isoform in brain. We have studied transgenic mice overexpressing type I NRG1(NRG1type 1-tg) using a(More)
Two proteolipid proteins, PLP and DM20, are the major membrane components of central nervous system (CNS) myelin. Mutations of the X-linked PLP/DM20 gene cause dysmyelination in mouse and man and result in significant mortality. Here we show that mutant mice that lack expression of a targeted PLP gene fail to exhibit the known dysmyelinated phenotype.(More)
Glial cells produce myelin and contribute to axonal morphology in the nervous system. Two myelin membrane proteolipids, PLP and DM20, were shown to be essential for the integrity of myelinated axons. In the absence of PLP-DM20, mice assembled compact myelin sheaths but subsequently developed widespread axonal swellings and degeneration, associated(More)
The transcription factors neuronal helix-loop-helix protein (NEX)/mammalian atonal homolog 2 (Math-2), BETA2/neuronal determination factor (NeuroD), and NeuroD-related factor (NDRF)/NeuroD2 comprise a family of Drosophila atonal-related basic helix-loop-helix (bHLH) proteins with highly overlapping expression in the developing forebrain. The ability of(More)
Understanding the control of myelin formation by oligodendrocytes is essential for treating demyelinating diseases. Neuregulin-1 (NRG1) type III, an EGF-like growth factor, is essential for myelination in the PNS. It is thus thought that NRG1/ErbB signaling also regulates CNS myelination, a view suggested by in vitro studies and the overexpression of(More)
Neural progenitor proliferation, differentiation and migration are continually active in the rostral migratory stream of the adult brain. Here, we show that the receptor tyrosine kinase ErbB4 is expressed prominently by the neuroblasts present in the subventricular zone and the rostral migratory stream. The neuregulins (NRG1-NRG3), which have been(More)