β1 Integrins in Muscle, But Not in Motor Neurons, Are Required for Skeletal Muscle Innervation

Abstract

In vitrostudies have provided evidence thatβ1 integrins in motor neurons promote neurite outgrowth, whereasβ1 integrins in myotubes regulate acetylcholine receptor (AChR) clustering. Surprisingly, using genetic studies in mice, we show here that motor axon outgrowth and neuromuscular junction (NMJ) formation in large part are unaffected when the integrin β1 gene (Itgb1) is inactivated in motor neurons. In the absence ofItgb1expression in skeletal muscle, interactions between motor neurons and muscle are defective, preventing normal presynaptic differentiation. Motor neurons fail to terminate their growth at the muscle midline, branch excessively, and develop abnormal nerve terminals. These defects resemble the phenotype of agrin-null mice, suggesting that signaling molecules such as agrin, which coordinate presynaptic and postsynaptic differentiation, are not presented properly to nerve terminals. We conclude thatItgb1expression in muscle, but not in motor neurons, is critical for NMJ development.