p75-deficient trigeminal sensory neurons have an altered response to NGF but not to other neurotrophins.
The role of the common low affinity neurotrophin receptor, p75, is controversial. Studies using cell lines suggest that p75 is either essential or dispensable for neurotrophin responsiveness. To resolve this issue, we studied the survival response of developing neurons obtained from normal mouse embryos and embryos with a null mutation in the p75 gene. Embryonic cranial sensory and sympathetic neurons from mutant embryos responded normally to NGF, BDNF, NT-3, and NT-4/5 at saturating concentrations. Dose responses of sympathetic and visceral sensory neurons from mutant embryos were also normal. In contrast, embryonic cutaneous sensory trigeminal neurons isolated from mutant embryos displayed a consistent displacement in the NGF dose response. Compared with wild-type neurons, the concentration of NGF that promoted half-maximal survival was 3- to 4-fold higher for neurons from homozygous embryos and was 2-fold higher for neurons from heterozygous embryos. These findings indicate that p75 enhances the sensitivity of NGF-dependent cutaneous sensory neurons to NGF and may explain, at least in part, the cutaneous sensory abnormalities of mice homozygous for the p75 mutation.
School of Biological and Medical Sciences, University of St. Andrews, Fife, Scotland.
A M
AM
Davies
K F
KF
Lee
R
R
Jaenisch
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003433:Crosses, Genetic; D004622:Embryo, Mammalian; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000166:cytology* / Q000187:drug effects; D020933:Neurotrophin 3; D009620:Nodose Ganglion / Q000166:cytology*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology*
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor