Abnormal enwrapment of intramuscular axons by distal Schwann cells with defective basal lamina in the muscular dysgenic mouse embryo.
In the muscular dysgenic (mdg/mdg) mouse embryo, both muscle and nerve are affected early during embryogenesis, from Embryonic Day 13 (E13). We now find that the mutation affects not only the degree of differentiation of the muscle and the pattern of motor innervation but also the relationship between Schwann cell and axon. We studied the sciatic nerve of normal and mdg/mdg embryos between E13 and E18 at the ultrastructural level. We found that in mdg/mdg nerve, (1) Schwann cells do not totally enwrap the growing axons in their most distal part, close to the growth cone, and (2) the terminal Schwann cells do not correctly surround the nerve endings and seal the corresponding synaptic contacts. Moreover, both types of mutant Schwann cell lack a normal electron-dense basal lamina. We found that there is an excess of axons relative to the Schwann cell population in the intramuscular portions of the mdg/mdg sciatic nerve. Our observations point toward a possible defect of the mechanism of migration and maturation of Schwann cells. Such a defect may in turn affect primarily or secondarily the mutual influences between Schwann cell and axon and lead to some or all of the major abnormalities observed in the mdg/mdg neuromuscular system, namely, multifocal polyinnervation, immature axon-myotube contacts, and abnormal T-tubule-sarcoplasmic reticulum junctions.
Pinçon-Raymond
M
M
UA 614 CNRS, U. 153 INSERM, Paris, France.
Murawsky
M
M
Mege
R M
RM
Rieger
F
F
D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D001485:Basement Membrane / Q000648:ultrastructure; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009132:Muscles / Q000002:abnormalities* / Q000196:embryology / Q000294:innervation / Q000648:ultrastructure; D009412:Nerve Fibers / Q000648:ultrastructure; D012583:Schwann Cells / Q000648:ultrastructure*; D012584:Sciatic Nerve / Q000196:embryology / Q000648:ultrastructure; D013569:Synapses / Q000648:ultrastructure