Assembly of the auditory circuitry by a Hox genetic network in the mouse brainstem

• Published in: PLoS genetics 2013-02, Vol.9 (2), p.e1003249-e1003249
• Main Authors: Di Bonito, Maria, Narita, Yuichi, Avallone, Bice, Sequino, Luigi, Mancuso, Marta, Andolfi, Gennaro, Franzè, Anna Maria, Puelles, Luis, Rijli, Filippo M, Studer, Michèle
• Format: Article
• Language: English
• Subjects: Animals; Auditory cortex; Auditory Pathways - metabolism; Auditory Pathways - physiology; Axons - metabolism; Biology; Brain Stem - growth & development; Brain Stem - metabolism; Cochlea - growth & development; Cochlea - metabolism; DEAD Box Protein 58; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Development Biology; Ears & hearing; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Genetic aspects; Genetic code; Grants; Hair; Health aspects; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Hox genes; Life Sciences; Mice; Midline Thalamic Nuclei - growth & development; Midline Thalamic Nuclei - metabolism; Motor Neurons - cytology; Motor Neurons - metabolism; Olivary Nucleus - growth & development; Olivary Nucleus - metabolism; Physiological aspects; Rodents; Sound; Sound Localization; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1003249

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.