6533b86efe1ef96bd12cb653
RESEARCH PRODUCT
Erbb2 regulates neuromuscular synapse formation and is essential for muscle spindle development
Ulrich MüllerUlrich MüllerMartin SchwanderMarco LeuHans Rudolf BrennerIsabel FariñasElena Bellmuntsubject
Receptor ErbB-2Muscle spindleNeuromuscular JunctionMice TransgenicBiologySynaptic TransmissionNeuromuscular junctionSynapseMiceErbB ReceptorsmedicineAnimalsHumansMuscle SkeletalPromoter Regions Geneticskin and connective tissue diseasesMuscle SpindlesMolecular BiologyAcetylcholine receptorMice KnockoutAfferent PathwaysMyogenesisGenes erbB-2ActinsMice Mutant StrainsCell biologyMice Inbred C57BLmedicine.anatomical_structureSilent synapseNeuregulinSignal TransductionDevelopmental Biologydescription
Neuregulins and their Erbb receptors have been implicated in neuromuscular synapse formation by regulating gene expression in subsynaptic nuclei. To analyze the function of Erbb2 in this process, we have inactivated the Erbb2 gene in developing muscle fibers by Cre/Lox-mediated gene ablation. Neuromuscular synapses form in the mutant mice, but the synapses are less efficient and contain reduced levels of acetylcholine receptors. Surprisingly, the mutant mice also show proprioceptive defects caused by abnormal muscle spindle development. Sensory Ia afferent neurons establish initial contact with Erbb2-deficient myotubes. However, functional spindles never develop. Taken together, our data suggest that Erbb2 signaling regulates the formation of both neuromuscular synapses and muscle spindles.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-06-01 | Development |