Dorsal root ganglion neurons require functional neurotrophin receptors for survival during development.
Neurotrophins are the most profound known regulators of survival in the developing peripheral nervous system. Within dorsal root ganglia, the signalling receptors for the different members of the neurotrophin family are distributed in distinct patterns suggesting regulation of different functional classes of sensory neurons. Abnormalities observed in neurotrophin receptor mutant mice have confirmed this idea. Both trkA (-/-) and trkC (-/-) mice have striking neurological defecits referrable to subpopulations of DRG neurons which have distinct axon projections in the periphery. These results thus generalize concepts of dependence on target-derived factors based on extensive work with the prototypical neurotrophin, nerve growth factor. Further analysis of these animals also provides evidence for more complex developmental mechanisms including dependence on locally synthesized neurotrophins at early developmental stages and plasticity of neurotrophin receptor expression.
Snider
W D
WD
Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Silos-Santiago
I
I
D000818:Animals; D002470:Cell Survival; D015536:Down-Regulation; D005727:Ganglia, Spinal / Q000196:embryology / Q000254:growth & development*; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D020917:Receptor, trkA; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D011518:Proto-Oncogene Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020812:Receptor, trkC