Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea

• DOI: 10.1073/pnas.0808175105
• Publication Date: 2008-11-15T01:54:26Z
• Authors: Alain Dabdoub; Chandrakala Pulig...; Jennifer M. Jones; Bernd Fritzsch; Kathryn S. E. Cheah; Larysa H. Pevny; Matthew W. Kelley
• Keywords: 570; 0303 health sciences; Hair Cells, Auditory, Inner; Receptors, Notch; SOXB1 Transcription Factors; Inner - cytology; Receptors, Notch - metabolism; Cell Differentiation; Notch - metabolism; SOXB1 Transcription Factors - metabolism; Cochlea - cytology - growth & development; Hair Cells, Auditory, Inner - cytology; Cochlea; Mice; 03 medical and health sciences; Hair Cells; Receptors; Animals; Auditory; Signal Transduction

Sox2 is a high-mobility transcription factor that one of the earliest markers developing inner ear prosensory domains. In humans, mutations in SOX2 cause sensorineural hearing loss and function study mice showed required for formation cochlea. However, specific roles have not been determined. Here we illustrate dynamic role as an early permissive domain followed by mutually antagonistic relationship with Atoh1, bHLH protein necessary hair cell development. We demonstrate decreased levels result precocious differentiation over production cells these effects are likely mediated through interaction between molecule Atoh1. Using gain- loss-of-function experiments provide evidence molecular pathway responsible cochlear domain. expression promoted Notch signaling Prox1, homeobox factor, downstream target Sox2. These results crucial diverse development, specification, maintenance sensory within