Atoh1-Lineal Neurons Are Required for Hearing and for the Survival of Neurons in the Spiral Ganglion and Brainstem Accessory Auditory Nuclei

• Published in: The Journal of neuroscience Vol. 29; no. 36; pp. 11123 - 11133
• Main Authors: Maricich, Stephen M, Xia, Anping, Mathes, Erin L, Wang, Vincent Y, Oghalai, John S, Fritzsch, Bernd, Zoghbi, Huda Y
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 09-09-2009; Society for Neuroscience
• Subjects: Acoustic Stimulation - methods; Animals; Animals, Newborn; Basic Helix-Loop-Helix Transcription Factors - deficiency; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - physiology; Brain Stem - pathology; Brain Stem - physiology; Cell Survival - physiology; Cochlear Nucleus - pathology; Cochlear Nucleus - physiology; Female; Hearing - genetics; Hearing - physiology; Mice; Mice, Congenic; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Neurons - pathology; Neurons - physiology; Pregnancy; Spiral Ganglion - pathology; Spiral Ganglion - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.2232-09.2009

Atoh1 is a basic helix-loop-helix transcription factor necessary for the specification of inner ear hair cells and central auditory system neurons derived from the rhombic lip. We used the Cre-loxP system and two Cre-driver lines (Egr2(Cre) and Hoxb1(Cre)) to delete Atoh1 from different regions of the cochlear nucleus (CN) and accessory auditory nuclei (AAN). Adult Atoh1-conditional knock-out mice (Atoh1(CKO)) are behaviorally deaf, have diminished auditory brainstem evoked responses, and have disrupted CN and AAN morphology and connectivity. In addition, Egr2; Atoh1(CKO) mice lose spiral ganglion neurons in the cochlea and AAN neurons during the first 3 d of life, revealing a novel critical period in the development of these neurons. These new mouse models of predominantly central deafness illuminate the importance of the CN for support of a subset of peripheral and central auditory neurons.