Beta1 integrins in muscle, but not in motor neurons, are required for skeletal muscle innervation.
In vitro studies have provided evidence that beta1 integrins in motor neurons promote neurite outgrowth, whereas beta1 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 beta1 gene (Itgb1) is inactivated in motor neurons. In the absence of Itgb1 expression 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 that Itgb1 expression in muscle, but not in motor neurons, is critical for NMJ development.
Schwander
Martin
M
Department of Cell Biology and Institute for Childhood and Neglected Disease, The Scripps Research Institute, La Jolla, California 92037, USA.
Shirasaki
Ryuichi
R
Pfaff
Samuel L
SL
Müller
Ulrich
U
D018171:Agrin / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D017353:Gene Deletion; D018390:Gene Targeting; D005804:Genes, Lethal; D019426:Integrases / Q000502:physiology; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009046:Motor Neurons / Q000737:chemistry / Q000502:physiology*; D009123:Muscle Hypotonia / Q000151:congenital / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000294:innervation*; D009419:Nerve Tissue Proteins / Q000502:physiology; D009469:Neuromuscular Junction / Q000737:chemistry / Q000196:embryology* / Q000473:pathology; D009928:Organ Specificity; D010525:Peripheral Nerves / Q000196:embryology; D017729:Presynaptic Terminals / Q000737:chemistry / Q000502:physiology; D011950:Receptors, Cholinergic / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013116:Spinal Cord / Q000196:embryology; D014764:Viral Proteins / Q000502:physiology
D018171:Agrin; D019012:Integrin beta1; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D011950:Receptors, Cholinergic; D011994:Recombinant Proteins; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases