SOX2 is required for inner ear growth and cochlear nonsensory formation prior to sensory development

• Published in: Development (Cambridge)
• Main Authors: Steevens, Aleta R., Glatzer, Jenna C., Kellogg, Courtney C., Low, Walter C., Santi, Peter A., Kiernan, Amy E.
• Format: Journal Article
• Language: English
• Published: 01.01.2019
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.170522

The transcription factor SOX2 is required for the formation of hair cells and supporting cells in the inner ear and is a widely used sensory marker. Paradoxically, we demonstrate via fate-mapping that initially SOX2 primarily marks nonsensory progenitors in the cochlea, and is not specific to all sensory regions until late otic vesicle stages. SOX2 fate-mapping reveals an apical-to-basal gradient of SOX2 expression in the sensory region of the cochlea, reflecting the pattern of cell cycle exit. To understand SOX2 function, we undertook a timed-deletion approach, revealing that early loss of SOX2 severely impaired morphological development of the ear; whereas later deletions resulted in sensory disruptions. During otocyst stages SOX2 shifted dramatically from a lateral to medial domain over 24-48hrs, reflecting the nonsensory-to-sensory switch observed by fate-mapping. Early loss or gain of SOX2 function leads to changes in otic epithelial volume and progenitor proliferation, impacting growth and morphological development of the ear. Our study demonstrates a novel role for SOX2 in early otic morphological development, and provides insights into the temporal and spatial patterns of sensory specification in the inner ear.