title: Assembly of the auditory circuitry by a Hox genetic network in the mouse brainstem.
abstract: Rhombomeres (r) contribute to brainstem auditory nuclei during development. Hox genes are determinants of rhombomere-derived fate and neuronal connectivity. Little is known about the contribution of individual rhombomeres and their associated Hox codes to auditory sensorimotor circuitry. Here, we show that r4 contributes to functionally linked sensory and motor components, including the ventral nucleus of lateral lemniscus, posterior ventral cochlear nuclei (VCN), and motor olivocochlear neurons. Assembly of the r4-derived auditory components is involved in sound perception and depends on regulatory interactions between Hoxb1 and Hoxb2. Indeed, in Hoxb1 and Hoxb2 mutant mice the transmission of low-level auditory stimuli is lost, resulting in hearing impairments. On the other hand, Hoxa2 regulates the Rig1 axon guidance receptor and controls contralateral projections from the anterior VCN to the medial nucleus of the trapezoid body, a circuit involved in sound localization. Thus, individual rhombomeres and their associated Hox codes control the assembly of distinct functionally segregated sub-circuits in the developing auditory brainstem.
authors: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors: Maria
authors: M
authors: Di Bonito
authors: Yuichi
authors: Y
authors: Narita
authors: Bice
authors: B
authors: Avallone
authors: Luigi
authors: L
authors: Sequino
authors: Marta
authors: M
authors: Mancuso
authors: Gennaro
authors: G
authors: Andolfi
authors: Anna Maria
authors: AM
authors: Franzè
authors: Luis
authors: L
authors: Puelles
authors: Filippo M
authors: FM
authors: Rijli
authors: Michèle
authors: M
authors: Studer
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000378:metabolism / Q000502:physiology; D001369:Axons / Q000378:metabolism; D001933:Brain Stem / Q000254:growth & development / Q000378:metabolism; D003051:Cochlea / Q000254:growth & development / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D020644:Midline Thalamic Nuclei / Q000254:growth & development / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009847:Olivary Nucleus / Q000254:growth & development / Q000378:metabolism; D013017:Sound Localization; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C101121:HOXB1 homeodomain protein; D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse; C490111:Hoxb2 protein, mouse; D014157:Transcription Factors; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases