Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Woldeyesus MT
,
Britsch S
,
Riethmacher D
,
Xu L
,
Sonnenberg-Riethmacher E
,
Abou-Rebyeh F
,
Harvey R
,
Caroni P
,
Birchmeier C
.
???displayArticle.abstract???
The ErbB2 tyrosine kinase functions as coreceptor for the neuregulin receptors ErbB3 and ErbB4 and can participate in signaling of EGF receptor (ErbB1), interleukin receptor gp130, and G-protein coupled receptors. ErbB2(-/-) mice die at midgestation because of heart malformation. Here, we report a genetic rescue of their heart development by myocardial expression of erbB2 cDNA that allows survival of the mutants to birth. In rescued erbB2 mutants, Schwann cells are lacking. Motoneurons form and can project to muscle, but nerves are poorly fasciculated and disorganized. Neuromuscular junctions form, as reflected in clustering of AChR and postsynaptic expression of the genes encoding the alpha-AChR, AChE, epsilon-AChR, and the RI subunit of the cAMP protein kinase. However, a severe loss of motoneurons on cervical and lumbar, but not on thoracic levels occurs. Our results define the roles of Schwann cells during motoneuron and synapse development, and reveal different survival requirements for distinct motoneuron populations.
???displayArticle.pubmedLink???
10521398
???displayArticle.pmcLink???PMC317072 ???displayArticle.link???Genes Dev
Altiok,
ErbB3 and ErbB2/neu mediate the effect of heregulin on acetylcholine receptor gene expression in muscle: differential expression at the endplate.
1995, Pubmed
Altiok,
ErbB3 and ErbB2/neu mediate the effect of heregulin on acetylcholine receptor gene expression in muscle: differential expression at the endplate.
1995,
Pubmed
Balice-Gordon,
Dynamic roles at the neuromuscular junction. Schwann cells.
1996,
Pubmed
Bargmann,
Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185.
1986,
Pubmed
Britsch,
The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for development of the sympathetic nervous system.
1998,
Pubmed
Bunge,
Expanding roles for the Schwann cell: ensheathment, myelination, trophism and regeneration.
1993,
Pubmed
Burden,
Neuregulins and their receptors: a versatile signaling module in organogenesis and oncogenesis.
1997,
Pubmed
Carraway,
A neu acquaintance for erbB3 and erbB4: a role for receptor heterodimerization in growth signaling.
1994,
Pubmed
Daub,
Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors.
1996,
Pubmed
DeChiara,
The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo.
1996,
Pubmed
Erickson,
ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice.
1997,
Pubmed
Falls,
ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family.
1993,
Pubmed
Fischbach,
ARIA: a neuromuscular junction neuregulin.
1997,
Pubmed
Fromm,
Synapse-specific and neuregulin-induced transcription require an ets site that binds GABPalpha/GABPbeta.
1998,
Pubmed
Gassmann,
Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor.
1995,
Pubmed
Gautam,
Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice.
1995,
Pubmed
Gautam,
Defective neuromuscular synaptogenesis in agrin-deficient mutant mice.
1996,
Pubmed
Glass,
Agrin acts via a MuSK receptor complex.
1996,
Pubmed
Goldman,
Heterodimerization of the erbB-1 and erbB-2 receptors in human breast carcinoma cells: a mechanism for receptor transregulation.
1990,
Pubmed
Grieshammer,
Muscle-specific cell ablation conditional upon Cre-mediated DNA recombination in transgenic mice leads to massive spinal and cranial motoneuron loss.
1998,
Pubmed
Holmes,
Identification of heregulin, a specific activator of p185erbB2.
1992,
Pubmed
Imaizumi-Scherrer,
Accumulation in fetal muscle and localization to the neuromuscular junction of cAMP-dependent protein kinase A regulatory and catalytic subunits RI alpha and C alpha.
1996,
Pubmed
Jo,
Neuregulins are concentrated at nerve-muscle synapses and activate ACh-receptor gene expression.
1995,
Pubmed
Kraus,
Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors.
1989,
Pubmed
Lee,
Requirement for neuregulin receptor erbB2 in neural and cardiac development.
1995,
Pubmed
Lenferink,
Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers.
1998,
Pubmed
Lints,
Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants.
1993,
Pubmed
Lyons,
Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5.
1995,
Pubmed
Marchionni,
Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system.
1993,
Pubmed
Massoulié,
Acetylcholinesterase: C-terminal domains, molecular forms and functional localization.
1998,
Pubmed
McMahan,
The agrin hypothesis.
1990,
Pubmed
McManaman,
Rescue of motoneurons from cell death by a purified skeletal muscle polypeptide: effects of the ChAT development factor, CDF.
1990,
Pubmed
Meyer,
Multiple essential functions of neuregulin in development.
1995,
Pubmed
Missias,
Maturation of the acetylcholine receptor in skeletal muscle: regulation of the AChR gamma-to-epsilon switch.
1996,
Pubmed
Moscoso,
Synapse-associated expression of an acetylcholine receptor-inducing protein, ARIA/heregulin, and its putative receptors, ErbB2 and ErbB3, in developing mammalian muscle.
1995,
Pubmed
Naciff,
Molecular characterization of the mouse vesicular acetylcholine transporter gene.
1997,
Pubmed
Parmantier,
Schwann cell-derived Desert hedgehog controls the development of peripheral nerve sheaths.
1999,
Pubmed
Pinkas-Kramarski,
ErbB tyrosine kinases and the two neuregulin families constitute a ligand-receptor network.
1998,
Pubmed
Plowman,
Molecular cloning and expression of an additional epidermal growth factor receptor-related gene.
1990,
Pubmed
Qiu,
Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells.
1998,
Pubmed
Riese,
Specificity within the EGF family/ErbB receptor family signaling network.
1998,
Pubmed
Riethmacher,
Severe neuropathies in mice with targeted mutations in the ErbB3 receptor.
1997,
Pubmed
Rimer,
Neuregulins and erbB receptors at neuromuscular junctions and at agrin-induced postsynaptic-like apparatus in skeletal muscle.
1998,
Pubmed
Sandrock,
Maintenance of acetylcholine receptor number by neuregulins at the neuromuscular junction in vivo.
1997,
Pubmed
Sanes,
Development of the vertebrate neuromuscular junction.
1999,
Pubmed
Schaeffer,
Implication of a multisubunit Ets-related transcription factor in synaptic expression of the nicotinic acetylcholine receptor.
1998,
Pubmed
Son,
Schwann cells induce and guide sprouting and reinnervation of neuromuscular junctions.
1996,
Pubmed
Tsuchida,
Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes.
1994,
Pubmed
Tzahar,
The ErbB-2/HER2 oncogenic receptor of adenocarcinomas: from orphanhood to multiple stromal ligands.
1998,
Pubmed
Ullian,
The Schwann song of the glia-less synapse.
1998,
Pubmed
Weiss,
Novel mechanisms of RTK signal generation.
1997,
Pubmed
Wen,
Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit.
1992,
Pubmed
Witzemann,
Neural factors regulate AChR subunit mRNAs at rat neuromuscular synapses.
1991,
Pubmed
Yamamoto,
Hepatocyte growth factor (HGF/SF) is a muscle-derived survival factor for a subpopulation of embryonic motoneurons.
1997,
Pubmed
Zhu,
Neuregulin receptors, erbB3 and erbB4, are localized at neuromuscular synapses.
1995,
Pubmed