p75 is important for axon growth and schwann cell migration during development.
Mice lacking the low-affinity neurotrophin receptor p75 have multiple peripheral neural deficits. Here we examined the developmental nature of these deficiencies. Peripheral axons in p75 -/- embryos were severely stunted and poorly arborized from embryonic day 11.5 (E11.5) to E14.5. In vitro, neurite outgrowth from the dorsal root ganglia was significantly decreased in the p75 -/- embryos at E12.5, suggesting that stunted axonal growth in the embryo may result in part from defects in neurite elongation. Additionally, Schwann cell marker S100beta immunoreactivity was decreased or absent along the growing axons of the ophthalmic branch from the trigeminal ganglia in p75 -/- embryos. Electron microscopy studies of the axons of the trigeminal ganglion at E13.5 revealed that in the p75 mutant embryo, nerve bundles were highly impaired and that coverage of the growing axons by Schwann cell cytoplasm was substantially reduced. In vitro, Schwann cell migration from the dorsal root ganglia was significantly decreased in the p75 -/- embryos at E12.5, suggesting that the lack of S100beta staining and Schwann cell coverage in the p75 mutant results from a deficit in Schwann cell migration. These results provide evidence that p75 is important in the developing embryo for regulating axon growth and arborization and for Schwann cell migration.
Bentley
C A
CA
The Salk Institute, La Jolla, California 92037, USA.
Lee
K F
KF
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D004622:Embryo, Mammalian / Q000294:innervation / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009414:Nerve Growth Factors / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020800:Receptor, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012583:Schwann Cells / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D012668:Trigeminal Ganglion / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D014404:Tubulin / Q000378:metabolism
D002135:Calcium-Binding Proteins; D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D014404:Tubulin