title: BMP7-induced dendritic growth in sympathetic neurons requires p75(NTR) signaling.
abstract: Dendritic morphology is a critical determinant of neuronal connectivity, and in postganglionic sympathetic neurons, tonic activity correlates directly with the size of the dendritic arbor. Thus, identifying signaling mechanisms that regulate dendritic arborization of sympathetic neurons is important to understanding how functional neural circuitry is established and maintained in the sympathetic nervous system. Bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, downstream signaling events that link BMP receptor activation to dendritic growth are poorly characterized. We previously reported that BMP7 upregulates p75(NTR) mRNA in cultured sympathetic neurons. This receptor is implicated in controlling dendritic growth in central neurons but whether p75(NTR) regulates dendritic growth in peripheral neurons is not known. Here, we demonstrate that BMP7 increases p75(NTR) protein in cultured sympathetic neurons, and this effect is blocked by pharmacologic inhibition of signaling via BMP type I receptor. BMP7 does not trigger dendritic growth in sympathetic neurons dissociated from superior cervical ganglia (SCG) of p75(NTR) nullizygous mice, and overexpression of p75(NTR) in p75(NTR) -/- neurons is sufficient to cause dendritic growth even in the absence of BMP7. Morphometric analyses of SCG from wild-type versus p75(NTR) nullizygous mice at 3, 6, and 12 to 16 weeks of age indicated that genetic deletion of p75(NTR) does not prevent dendritic growth but does stunt dendritic maturation in sympathetic neurons. These data support the hypotheses that p75(NTR) is involved in downstream signaling events that mediate BMP7-induced dendritic growth in sympathetic neurons, and suggest that p75(NTR) signaling positively modulates dendritic complexity in sympathetic neurons in vivo. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1003-1013, 2016.
authors.affiliation: Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, Oregon, 97239.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Courter
authors.affiliation: Department of Molecular Biosciences, University of California, Davis, California, 95616.
authors.forename: Frances C
authors.initials: FC
authors.lastname: Shaffo
authors.affiliation: Department of Molecular Biosciences, University of California, Davis, California, 95616.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Ghogha
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon, 97239.
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Parrish
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon, 97239.
authors.forename: Christina U
authors.initials: CU
authors.lastname: Lorentz
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon, 97239.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Habecker
authors.affiliation: Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, Oregon, 97239.|Department of Molecular Biosciences, University of California, Davis, California, 95616.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Lein
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000378:metabolism*
chemical_list: C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; C525820:bmp7 protein, mouse; C068313:Ngfr protein, rat
keywords: BMP7; dendrite; neuronal connectivity; p75NTR; sympathetic neuron