Atoh1-lineal neurons are required for hearing and for the survival of neurons in the spiral ganglion and brainstem accessory auditory nuclei.
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.
Maricich
Stephen M
SM
Department of Pediatrics and Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, USA. smm18@case.edu
Xia
Anping
A
Mathes
Erin L
EL
Wang
Vincent Y
VY
Oghalai
John S
JS
Fritzsch
Bernd
B
Zoghbi
Huda Y
HY
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001933:Brain Stem / Q000473:pathology / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D017626:Cochlear Nucleus / Q000473:pathology / Q000502:physiology; D005260:Female; D006309:Hearing / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D011247:Pregnancy; D013136:Spiral Ganglion / Q000473:pathology / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; C500943:Atoh1 protein, mouse