title: Nonneuronal cells regulate synapse formation in the vestibular sensory epithelium via erbB-dependent BDNF expression.
abstract: Recent studies indicate that molecules released by glia can induce synapse formation. However, what induces glia to produce such signals, their identity, and their in vivo relevance remain poorly understood. Here we demonstrate that supporting cells of the vestibular organ--cells that have many characteristics of glia--promote synapse formation only when induced by neuron-derived signals. Furthermore, we identify BDNF as the synaptogenic signal produced by these nonneuronal cells. Mice in which erbB signaling has been eliminated in supporting cells have vestibular dysfunction caused by failure of synapse formation between hair cells and sensory neurons. This phenotype correlates with reduced BDNF expression in supporting cells and is rescued by reexpression of BDNF in these cells. Furthermore, knockdown of BDNF expression in supporting cells postnatally phenocopies the loss of erbB signaling. These results indicate that vestibular supporting cells contribute in vivo to vestibular synapse formation and that this is mediated by reciprocal signals between sensory neurons and supporting cells involving erbB receptors and BDNF.
authors.affiliation: F. M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Gómez-Casati
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Murtie
authors.forename: Carlos
authors.initials: C
authors.lastname: Rio
authors.forename: Konstantina
authors.initials: K
authors.lastname: Stankovic
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
authors.forename: Gabriel
authors.initials: G
authors.lastname: Corfas
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004848:Epithelium / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein; D018069:Hair Cells, Vestibular / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009457:Neuroglia / Q000502:physiology*; D066247:Receptor, ErbB-4; D013569:Synapses / Q000502:physiology*; D014722:Vestibule, Labyrinth / Q000166:cytology / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4