Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 39, Pages 17005-17010Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1008938107
Keywords
erbB receptor signaling; glia; vestibular organ; glutamatergic synapse; hair cell
Categories
Funding
- National Institute on Deafness and Other Communication Disorders [R01 DC 004820, P30 DC 005209]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [P30-HD 18655]
- Pew Latin American Fellowship
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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.
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