Dorsal root ganglion neurons expressing trk are selectively sensitive to NGF deprivation in utero.
In utero immune deprivation of the neurotrophic molecule nerve growth factor (NGF) results in the death of most, but not all, mammalian dorsal root ganglion (DRG) neurons. The recent identification of trk, trkB, and trkC as the putative high affinity receptors for NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively, has allowed an examination of whether their expression by DRG neurons correlates with differential sensitivity to immune deprivation of NGF. In situ hybridization demonstrates that virtually all neurons expressing trk are lost during in utero NGF deprivation. Most, if not all, neurons expressing trkB and trkC survive this treatment. In contrast, the low affinity NGF receptor, p75NGFR, is expressed in both NGF deprivation-resistant and -sensitive neurons. These experiments show that DRG neurons expressing trk require NGF for survival. Furthermore, at least some of the DRG neurons that do not require NGF express the high affinity receptor for another neurotrophin. Finally, these experiments provide evidence that trk, and not p75NGFR, is the primary effector of NGF action in vivo.
Carroll
S L
SL
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Silos-Santiago
I
I
Frese
S E
SE
Ruit
K G
KG
Milbrandt
J
J
Snider
W D
WD
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D004622:Embryo, Mammalian; D005260:Female; D005727:Ganglia, Spinal / Q000196:embryology / Q000502:physiology*; D015870:Gene Expression; D009414:Nerve Growth Factors / Q000276:immunology / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D014599:Uterus / Q000502:physiology
D000906:Antibodies; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA