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doi: 10.1242/10.1242/dev.00447

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Erbb2 regulates neuromuscular synapse formation and is essential for muscle spindle development

Marco Leu¹, Elena Bellmunt², Martin Schwander¹, Isabel Fariñas², Hans Rudolf Brenner³ and Ulrich Müller^1,*,

¹ Friedrich Miescher Institute for Biomedical Research, Maulbeerstr. 66, 4058 Basel, Switzerland
² Departamento de Biologia Celular, Universidad de Valencia, 46100 Burjassot, Spain
³ Department of Physiology, University of Basel, 4051 Switzerland
^* Present address: The Scripps Research Institute, 10550 North Torrey Pines Road, ICND 222, La Jolla, CA 92037, USA

Author for correspondence (e-mail: umueller{at}scripps.edu)

Accepted 3 February 2003

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.

Key words: Erbb2, Nrg1, Muscle spindle, Synapse, Neuromuscular junction, Mouse

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