Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Jul 5;91(14):6501–6505. doi: 10.1073/pnas.91.14.6501

The p75 nerve growth factor receptor mediates survival or death depending on the stage of sensory neuron development.

G L Barrett 1, P F Bartlett 1
PMCID: PMC44230  PMID: 8022812

Abstract

The function of the low-affinity nerve growth factor (NGF) receptor, p75NGFR, in regulating neuronal survival during development is unclear. The sensory deficit in mice with mutated p75NGFR suggests it is necessary for development of sensory neurons; however, whether it is required, in addition to trkA, for signal transduction or is more involved in localization of NGF is unresolved. In this study we demonstrate, in vitro, that lowering the levels of p75NGFR expression in sensory neurons with antisense oligonucleotides largely prevents the NGF-mediated survival of sensory neurons from embryonic day 12 and 15 mice but increases the survival of embryonic day 19 and postnatal day 2 sensory neurons in the absence of NGF. Thus, the p75NGFR is required for NGF-mediated survival in neurons at the stage of target innervation but can mediate an apoptotic signal at a later stage of cell development. Thus, p75NGFR undergoes a switch in function in the perinatal period: during embryogenesis it is required, probably with trkA, to mediate neuronal survival in the presence of NGF, but in the early postnatal period it acts as a constitutive death signal in the absence of NGF.

Full text

PDF
6501

Images in this article

6502Image
on p.6502
6503Image
on p.6503
6504Image
on p.6504

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agrawal S., Temsamani J., Tang J. Y. Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7595–7599. doi: 10.1073/pnas.88.17.7595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Battleman D. S., Geller A. I., Chao M. V. HSV-1 vector-mediated gene transfer of the human nerve growth factor receptor p75hNGFR defines high-affinity NGF binding. J Neurosci. 1993 Mar;13(3):941–951. doi: 10.1523/JNEUROSCI.13-03-00941.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Heller R. A., Song K., Fan N., Chang D. J. The p70 tumor necrosis factor receptor mediates cytotoxicity. Cell. 1992 Jul 10;70(1):47–56. doi: 10.1016/0092-8674(92)90532-h. [DOI] [PubMed] [Google Scholar]
  4. Hempstead B. L., Martin-Zanca D., Kaplan D. R., Parada L. F., Chao M. V. High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature. 1991 Apr 25;350(6320):678–683. doi: 10.1038/350678a0. [DOI] [PubMed] [Google Scholar]
  5. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  6. Jing S., Tapley P., Barbacid M. Nerve growth factor mediates signal transduction through trk homodimer receptors. Neuron. 1992 Dec;9(6):1067–1079. doi: 10.1016/0896-6273(92)90066-m. [DOI] [PubMed] [Google Scholar]
  7. Lee K. F., Li E., Huber L. J., Landis S. C., Sharpe A. H., Chao M. V., Jaenisch R. Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell. 1992 May 29;69(5):737–749. doi: 10.1016/0092-8674(92)90286-l. [DOI] [PubMed] [Google Scholar]
  8. Martin-Zanca D., Barbacid M., Parada L. F. Expression of the trk proto-oncogene is restricted to the sensory cranial and spinal ganglia of neural crest origin in mouse development. Genes Dev. 1990 May;4(5):683–694. doi: 10.1101/gad.4.5.683. [DOI] [PubMed] [Google Scholar]
  9. Miyawaki T., Uehara T., Nibu R., Tsuji T., Yachie A., Yonehara S., Taniguchi N. Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood. J Immunol. 1992 Dec 1;149(11):3753–3758. [PubMed] [Google Scholar]
  10. Murphy M., Reid K., Brown M. A., Bartlett P. F. Involvement of leukemia inhibitory factor and nerve growth factor in the development of dorsal root ganglion neurons. Development. 1993 Mar;117(3):1173–1182. doi: 10.1242/dev.117.3.1173. [DOI] [PubMed] [Google Scholar]
  11. Rabizadeh S., Oh J., Zhong L. T., Yang J., Bitler C. M., Butcher L. L., Bredesen D. E. Induction of apoptosis by the low-affinity NGF receptor. Science. 1993 Jul 16;261(5119):345–348. doi: 10.1126/science.8332899. [DOI] [PubMed] [Google Scholar]
  12. Sariola H., Saarma M., Sainio K., Arumäe U., Palgi J., Vaahtokari A., Thesleff I., Karavanov A. Dependence of kidney morphogenesis on the expression of nerve growth factor receptor. Science. 1991 Oct 25;254(5031):571–573. doi: 10.1126/science.1658930. [DOI] [PubMed] [Google Scholar]
  13. Stemple D. L., Anderson D. J. Isolation of a stem cell for neurons and glia from the mammalian neural crest. Cell. 1992 Dec 11;71(6):973–985. doi: 10.1016/0092-8674(92)90393-q. [DOI] [PubMed] [Google Scholar]
  14. Wright E. M., Vogel K. S., Davies A. M. Neurotrophic factors promote the maturation of developing sensory neurons before they become dependent on these factors for survival. Neuron. 1992 Jul;9(1):139–150. doi: 10.1016/0896-6273(92)90229-7. [DOI] [PubMed] [Google Scholar]
  15. Yip H. K., Rich K. M., Lampe P. A., Johnson E. M., Jr The effects of nerve growth factor and its antiserum on the postnatal development and survival after injury of sensory neurons in rat dorsal root ganglia. J Neurosci. 1984 Dec;4(12):2986–2992. doi: 10.1523/JNEUROSCI.04-12-02986.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES