Erbb2 regulates neuromuscular synapse formation and is essential for muscle spindle development.
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.
Leu
Marco
M
Friedrich Miescher Institute for Biomedical Research, Maulbeerstr. 66, 4058 Basel, Switzerland.
Bellmunt
Elena
E
Schwander
Martin
M
Fariñas
Isabel
I
Brenner
Hans Rudolf
HR
Müller
Ulrich
U
D000199:Actins / Q000235:genetics; D000344:Afferent Pathways / Q000254:growth & development; D000818:Animals; D018734:Genes, erbB-2; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009470:Muscle Spindles / Q000254:growth & development* / Q000502:physiology; D018482:Muscle, Skeletal / Q000254:growth & development / Q000294:innervation; D009469:Neuromuscular Junction / Q000254:growth & development* / Q000502:physiology; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D009435:Synaptic Transmission
D000199:Actins; D018719:Erb-b2 Receptor Tyrosine Kinases