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The extracellular cues and signaling mechanisms that lead to the development of these specialized synaptic connections, exemplified by the calyx of Held in the medial nucleus of the trapezoid body (MNTB), are still largely unknown. Here, we investigate the role of BMP signaling for the early development of the ventral cochlear nucleus (VCN) and MNTB, and for the initial formation of the calyx of Held synaptic connection. We used conditional alleles of two BMP type\u20101 receptors in the background of a constitutive BMPR1b knock\u2010out (KO), or else a conditional allele of SMAD4. The conditional alleles were recombined by the Krox20\n                    <jats:sup>Cre<\/jats:sup>\n                    mouse line that is active around mid\u2010gestation in rhombomeres (r) 3 and 5 from which the VCN and MNTB are derived; alternatively, virus\u2010mediated Cre\u2010expression was performed early postnatally in the VCN. The data show that embryonic SMAD\u2010dependent BMP\u2010signaling in r3 and r5 contributes to the histogenesis of auditory brainstem nuclei. On the other hand, BMP\u2010receptor signaling early postnatally in presynaptic neurons of the calyx of Held projection is necessary for correct axon branch retraction, which suggests a cell\u2010autonomous role of presynaptic BMP\u2010receptors in synapse elimination at the developing calyx of Held. Thus, our work dissects developmentally early and late roles of BMP\u2010signaling for the formation of auditory brainstem nuclei, and the highly specialized synaptic connectivity in these structures.\n                  <\/jats:p>","DOI":"10.1002\/dneu.22661","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T13:20:52Z","timestamp":1544620852000},"page":"155-174","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Role of BMP Signaling for the Formation of Auditory Brainstem Nuclei and Large Auditory Relay Synapses"],"prefix":"10.1002","volume":"79","author":[{"given":"Elin","family":"Kronander","sequence":"first","affiliation":[{"name":"Laboratory of Synaptic Mechanisms, Brain Mind Institute, School of Life Science \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL) Lausanne 1015 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