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.

[1]  Wei Li,et al.  DNA topoisomerase IIβ and neural development , 2000 .

[2]  Marc Tessier-Lavigne,et al.  APP binds DR6 to trigger axon pruning and neuron death via distinct caspases , 2009, Nature.

[3]  S. Korsmeyer,et al.  BAX Is Required for Neuronal Death after Trophic Factor Deprivation and during Development , 1996, Neuron.

[4]  M. Chao,et al.  Competitive Signaling Between TrkA and p75 Nerve Growth Factor Receptors Determines Cell Survival , 1998, The Journal of Neuroscience.

[5]  D. Ginty,et al.  Growth and survival signals controlling sympathetic nervous system development. , 2005, Annual review of neuroscience.

[6]  R. Jaenisch,et al.  Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system , 1992, Cell.

[7]  R. Herbst,et al.  Restoration of synapse formation in Musk mutant mice expressing a Musk/Trk chimeric receptor , 2002, Development.

[8]  S. Burden,et al.  MuSK controls where motor axons grow and form synapses , 2008, Nature Neuroscience.

[9]  Xi Chen,et al.  A Chemical-Genetic Approach to Studying Neurotrophin Signaling , 2005, Neuron.

[10]  D. Ginty,et al.  Evidence in Support of Signaling Endosome-Based Retrograde Survival of Sympathetic Neurons , 2003, Neuron.

[11]  C. Howe,et al.  Long-distance retrograde neurotrophic signaling , 2005, Current Opinion in Neurobiology.

[12]  F. Rice,et al.  Development of Sensory Neurons in the Absence of NGF/TrkA Signaling In Vivo , 2000, Neuron.

[13]  H. Wichterle,et al.  Directed Differentiation of Embryonic Stem Cells into Motor Neurons , 2002, Cell.

[14]  D. Ginty,et al.  A Neurotrophin Signaling Cascade Coordinates Sympathetic Neuron Development through Differential Control of TrkA Trafficking and Retrograde Signaling , 2004, Cell.

[15]  F. Lee,et al.  A novel endocytic recycling signal distinguishes biological responses of Trk neurotrophin receptors. , 2005, Molecular biology of the cell.

[16]  J. W. Lichtman,et al.  Are Neurotrophins Synaptotrophins? , 1996, Molecular and Cellular Neuroscience.

[17]  T. Bonhoeffer,et al.  The p75 Neurotrophin Receptor Negatively Modulates Dendrite Complexity and Spine Density in Hippocampal Neurons , 2005, The Journal of Neuroscience.

[18]  R W Oppenheim,et al.  Cell death of motoneurons in the chick embryo spinal cord. V. Evidence on the role of cell death and neuromuscular function in the formation of specific peripheral connections , 1981, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  D. Ginty,et al.  Functions and mechanisms of retrograde neurotrophin signalling , 2005, Nature Reviews Neuroscience.

[20]  D. Purves.  Functional and structural changes in mammalian sympathetic neurones following interruption of their axons. , 1975, The Journal of physiology.

[21]  J. Wang,et al.  DNA topoisomerase IIbeta and neural development. , 2000, Science.

[22]  A. Markus,et al.  Neurotrophic factors and axonal growth , 2002, Current Opinion in Neurobiology.

[23]  L. C. Katz,et al.  Optical Imaging of Odorant Representations in the Mammalian Olfactory Bulb , 1999, Neuron.

[24]  R. Segal,et al.  Action in the axon: generation and transport of signaling endosomes , 2008, Current Opinion in Neurobiology.

[25]  G. Feng,et al.  PSD93 Regulates Synaptic Stability at Neuronal Cholinergic Synapses , 2004, The Journal of Neuroscience.

[26]  P. Distefano,et al.  The Receptor Tyrosine Kinase MuSK Is Required for Neuromuscular Junction Formation In Vivo , 1996, Cell.

[27]  M. von Zastrow,et al.  A Novel Endocytic Recycling Signal That Distinguishes the Membrane Trafficking of Naturally Occurring Opioid Receptors* , 2003, Journal of Biological Chemistry.

[28]  Yuyu Song,et al.  Axonal Transport Defects in Neurodegenerative Diseases , 2009, The Journal of Neuroscience.

[29]  D. Purves,et al.  Effect of nerve growth factor on synaptic depression after axotomy , 1976, Nature.

[30]  J. Sanes,et al.  Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse , 2001, Nature.

[31]  Michael E Greenberg,et al.  Developmental axon pruning mediated by BDNF-p75NTR–dependent axon degeneration , 2008, Nature Neuroscience.

[32]  Bai Lu,et al.  Activation of p75NTR by proBDNF facilitates hippocampal long-term depression , 2005, Nature Neuroscience.

[33]  S. Korsmeyer,et al.  Bax-Deficient Mice with Lymphoid Hyperplasia and Male Germ Cell Death , 1995, Science.

[34]  Mu-ming Poo,et al.  Neurotrophins as synaptic modulators , 2001, Nature Reviews Neuroscience.

[35]  C. Forehand.  Density of somatic innervation on mammalian autonomic ganglion cells is inversely related to dendritic complexity and preganglionic convergence , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  U J McMahan,et al.  Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites , 1978, The Journal of cell biology.

[37]  S. R. Wickramasinghe,et al.  Serum Response Factor Mediates NGF-Dependent Target Innervation by Embryonic DRG Sensory Neurons , 2008, Neuron.

[38]  R. Oppenheim.  Cell death of motoneurons in the chick embryo spinal cord. VIII. Motoneurons prevented from dying in the embryo persist after hatching. , 1984, Developmental biology.

[39]  C. Hoogenraad,et al.  The postsynaptic architecture of excitatory synapses: a more quantitative view. , 2007, Annual review of biochemistry.

[40]  C. Pozniak,et al.  The p75 Neurotrophin Receptor Mediates Neuronal Apoptosis and Is Essential for Naturally Occurring Sympathetic Neuron Death , 1998, The Journal of cell biology.

[41]  D. J. Wells,et al.  Cell death of motoneurons in the chick embryo spinal cord. VI. Reduction of naturally occurring cell death in the thoracolumbar column of terni by nerve growth factor , 1982, The Journal of comparative neurology.

[42]  M. von Zastrow,et al.  Identification of a Novel Endocytic Recycling Signal in the D1 Dopamine Receptor* , 2004, Journal of Biological Chemistry.

[43]  R. Freshney.  Animal cell culture : a practical approach , 1992 .

[44]  D. Ginty,et al.  Spatially and Functionally Distinct Roles of the PI3-K Effector Pathway during NGF Signaling in Sympathetic Neurons , 2000, Neuron.

[45]  Ernst Niebur,et al.  A model for neuronal competition during development , 2008, International Journal of Developmental Neuroscience.

[46]  D. Ginty,et al.  Heterogeneous Requirement of NGF for Sympathetic Target Innervation In Vivo , 2004, The Journal of Neuroscience.

[47]  E. Rubin.  Development of the rat superior cervical ganglion: initial stages of synapse formation , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[48]  N. Jeon,et al.  Microfluidic culture platform for neuroscience research , 2006, Nature Protocols.

[49]  S. McMahon,et al.  Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons , 1994, Cell.