Long-distance control of synapse assembly by target-derived NGF.
We report a role for long-distance retrograde neurotrophin signaling in the establishment of synapses in the sympathetic nervous system. Target-derived NGF is both necessary and sufficient for formation of postsynaptic specializations on dendrites of sympathetic neurons. This, in turn, is a prerequisite for formation of presynaptic specializations, but not preganglionic axonal ingrowth from the spinal cord into sympathetic ganglia. We also find that NGF-TrkA signaling endosomes travel from distal axons to cell bodies and dendrites where they promote PSD clustering. Furthermore, the p75 neurotrophin receptor restricts PSD formation, suggesting an important role for antagonistic NGF-TrkA and p75 signaling pathways during retrograde control of synapse establishment. Thus, in addition to defining the appropriate number of sympathetic neurons that survive the period of developmental cell death, target-derived NGF also exerts control over the degree of connectivity between the spinal cord and sympathetic ganglia through retrograde control of synapse assembly.
Sharma
Nikhil
N
The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Deppmann
Christopher D
CD
Harrington
Anthony W
AW
St Hillaire
Coryse
C
Chen
Zhe-Yu
ZY
Lee
Francis S
FS
Ginty
David D
DD
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D020800:Receptor, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D020917:Receptor, trkA / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000254:growth & development
D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA