Aberrant development of motor axons and neuromuscular synapses in erbB2-deficient mice.
Receptor tyrosine kinase erbB2, which is activated by neuregulin, is expressed in Schwann and muscle cells in the developing neuromuscular junction (NMJ). In vitro studies have shown that neuregulin promotes the survival and migration of Schwann cells and stimulates acetylcholine receptor gene transcription in cultured muscle cells. These findings suggest an important role for erbB2 in the development of the NMJ. Here we examine erbB2-deficient mice to determine whether erbB2 is required for NMJ development in vivo. Our analysis shows that there are pre- and postsynaptic defects of developing NMJ in erbB2-deficient embryos. The presynaptic defects include defasciculation and degeneration of the motor nerves, and an absence of Schwann cells. The postsynaptic defect features an impairment of junctional folds at the neuromuscular synapse in the mutants. These results demonstrate that erbB2 is essential for in vivo development of the NMJ.
Lin
W
W
The Salk Institute, La Jolla, CA 92037, USA.
Sanchez
H B
HB
Deerinck
T
T
Morris
J K
JK
Ellisman
M
M
Lee
K F
KF
D000818:Animals; D001369:Axons / Q000473:pathology*; D002465:Cell Movement; D003964:Diaphragm / Q000196:embryology / Q000473:pathology; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D018734:Genes, erbB-2; D017404:In Situ Hybridization, Fluorescence; D007366:Intercostal Muscles / Q000196:embryology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009024:Morphogenesis; D009046:Motor Neurons / Q000473:pathology*; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020880:Neuregulins / Q000502:physiology; D009469:Neuromuscular Junction / Q000002:abnormalities* / Q000196:embryology; D010791:Phrenic Nerve / Q000196:embryology / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000096:biosynthesis / Q000235:genetics; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology
D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D020880:Neuregulins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011950:Receptors, Cholinergic