The Erk MAP kinase pathway is activated at muscle spindles and is required for induction of the muscle spindle-specific gene Egr3 by neuregulin1.

Muscle spindles are sensory receptors composed of specialized muscle fibers, known as intrafusal muscle fibers, along with the endings of sensory neuron axons that innervate these muscle fibers. Formation of muscle spindles requires neuregulin1 (NRG1), which is released by sensory axons, activating ErbB receptors in muscle cells that are contacted. The transcription factor Egr3 is transcriptionally induced by NRG1, which in turn activates various target genes involved in forming intrafusal fibers.

Neuregulin1 signaling targets SRF and CREB and activates the muscle spindle-specific gene Egr3 through a composite SRF-CREB-binding site.

Muscle spindles are sensory receptors embedded within muscle that detect changes in muscle length. Each spindle is composed of specialized muscle fibers, known as intrafusal muscle fibers, along with the endings of axons from sensory neurons that innervate these muscle fibers. Formation of muscle spindles requires neuregulin1 (NRG1), which is released by sensory axons, activating ErbB receptors in muscle cells that are contacted.

Chromatin modifications that support acetylcholine receptor gene activation are established during muscle cell determination and differentiation.

Localization of acetylcholine receptors (AChRs) to the postsynaptic region of muscle is mediated in part by transcriptional mechanisms. An important way of regulating transcription is through targeting histone modifications on chromatin to distinct gene loci. Using chromatin immunoprecipitation, we examined the developmental regulation of certain histone modifications at the AChR epsilon subunit locus, including methylations at lysine residues K4 and K27 and acetylations at K9 and K14.

Neuregulin-1 induces acetylcholine receptor transcription in the absence of GABPalpha phosphorylation.

Localization of acetylcholine receptors (AChRs) to the postsynaptic region of muscle is mediated in part by transcriptional mechanisms, because the genes encoding AChR subunits are transcribed selectively in synaptic myofiber nuclei. Neuregulin-1 (NRG-1) is a synaptic signal and induces transcription of AChRs in muscle cells. Signaling by NRG-1 is thought to involve the transcription factor GA-binding protein (GABP), a heterodimer of GABPalpha, which is a member of the Ets family, and GABPbeta.

Directing RNA interference specifically to differentiated muscle cells.

A common approach for mediating RNA interference (RNAi) is to introduce DNA that encodes short hairpin RNA (shRNA), which is often contained in a plasmid that can express a shRNA in a wide variety of cell types. Muscle cells and certain other cell types grown in culture can exist in both a dividing state and in a post-mitotic, differentiated state, and it is sometimes useful to induce RNAi selectively in terminally differentiated cells to study the function of a gene, particularly when the gene is also required for propagation of dividing cells. We describe two methods for studying gene function by RNAi specifically in terminally differentiated skeletal muscle cells in culture.