Research article summary (published 9 Jan 2006):

Neuromuscular synapse formation in mice lacking motor neuron- and skeletal muscle-derived Neuregulin-1.

Full Abstract

The localization of acetylcholine receptors (AChRs) to the vertebrate neuromuscular junction is mediated, in part, through selective transcription of AChR subunit genes in myofiber subsynaptic nuclei. Agrin and the muscle-specific receptor tyrosine kinase, MuSK, have critical roles in synapse-specific transcription, because AChR genes are expressed uniformly in mice lacking either agrin or MuSK. Several lines of evidence suggest that agrin and MuSK stimulate synapse-specific transcription indirectly by regulating the distribution of other cell surface ligands, which stimulate a pathway for synapse-specific gene expression. This putative secondary signal for directing AChR gene expression to synapses is not known, but Neuregulin-1 (Nrg-1), primarily based on its presence at synapses and its ability to induce AChR gene expression in vitro, has been considered a good candidate. To study the role of Nrg-1 at neuromuscular synapses, we inactivated nrg-1 in motor neurons, skeletal muscle, or both cell types, using mice that express Cre recombinase selectively in developing motor neurons or in developing skeletal myofibers. We find that AChRs are clustered at synapses and that synapse-specific transcription is normal in mice lacking Nrg-1 in motor neurons, myofibers, or both cell types. These data indicate that Nrg-1 is dispensable for clustering AChRs and activating AChR genes in subsynaptic nuclei during development and suggest that these aspects of postsynaptic differentiation are dependent on Agrin/MuSK signaling without a requirement for a secondary signal.

Author information

Author/s: Jaworski, Alexander (A); Burden, Steven J (SJ);

Affiliation: Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2006-Jan; vol 26 (issue 2) : pp 655-61

Dates: Created 2006/01/12; Completed 2006/03/17; Revised 2008/11/21;

PMID: 16407563, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - physiology Animals Cell Differentiation Diaphragm - embryology; innervation Genes, Reporter Integrases - genetics; metabolism Intercostal Muscles - embryology; innervation Mice Mice, Knockout Motor Neurons - metabolism; ultrastructure Muscle Fibers, Skeletal - metabolism; ultrastructure Muscle, Skeletal - embryology; innervation

Muscle, Skeletal - embryology; innervation Nerve Tissue Proteins - deficiency; genetics; physiology Neuromuscular Junction - embryology; physiology; ultrastructure RNA, Messenger - biosynthesis; genetics Receptor Protein-Tyrosine Kinases - biosynthesis; genetics; physiology Receptor, Epidermal Growth Factor - metabolism Receptor, erbB-2 - metabolism Receptors, Cholinergic - biosynthesis; genetics; physiology Reverse Transcriptase Polymerase Chain Reaction Sequence Deletion Viral Proteins - genetics; metabolism beta-Galactosidase - analysis; genetics

Associated Chemicals: Agrin (0) ; Nerve Tissue Proteins (0) ; Nrg1 protein, mouse (0) ; RNA, Messenger (0) ; Receptors, Cholinergic (0) ; Viral Proteins (0) ; ERBB4 protein (EC 2.7.1.112) ; Receptor Protein-Tyrosine Kinases (EC 2.7.1.112) ; Receptor, Epidermal Growth Factor (EC 2.7.1.112) ; Receptor, erbB-2 (EC 2.7.1.112) ; MUSK protein, human (EC 2.7.10.1) ; Cre recombinase (EC 2.7.7.-) ; Integrases (EC 2.7.7.-) ; beta-Galactosidase (EC 3.2.1.23)

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