title: BMP signaling specifies the development of a large and fast CNS synapse.
abstract: Large excitatory synapses with multiple active zones ensure reliable and fast information transfer at specific points in neuronal circuits. However, the mechanisms that determine synapse size in CNS circuits are largely unknown. Here we use the calyx of Held synapse, a major relay in the auditory system, to identify and study signaling pathways that specify large nerve terminal size and fast synaptic transmission. Using genome-wide screening, we identified bone morphogenetic proteins (BMPs) as candidate signaling molecules in the area of calyx synapses. Conditional deletion of BMP receptors in the auditory system of mice led to aberrations of synapse morphology and function specifically at the calyx of Held, with impaired nerve terminal growth, loss of monoinnervation and less mature transmitter release properties. Thus, BMP signaling specifies large and fast-transmitting synapses in the auditory system in a process that shares homologies with, but also extends beyond, retrograde BMP signaling at Drosophila neuromuscular synapses.
authors.affiliation: Laboratory of Synaptic Mechanisms, Brain Mind Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Le
authors.initials: L
authors.lastname: Xiao
authors.forename: Nicolas
authors.initials: N
authors.lastname: Michalski
authors.forename: Elin
authors.initials: E
authors.lastname: Kronander
authors.forename: Enida
authors.initials: E
authors.lastname: Gjoni
authors.forename: Christel
authors.initials: C
authors.lastname: Genoud
authors.forename: Graham
authors.initials: G
authors.lastname: Knott
authors.forename: Ralf
authors.initials: R
authors.lastname: Schneggenburger
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000172:deficiency; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology* / Q000254:growth & development*; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development; D051767:Early Growth Response Protein 2 / Q000235:genetics; D004558:Electric Stimulation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D012249:Rhombencephalon / Q000166:cytology / Q000254:growth & development; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D019485:Bone Morphogenetic Proteins; D002135:Calcium-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D009419:Nerve Tissue Proteins; C498212:Bmpr1a protein, mouse; C498215:Bmpr1b protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I