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

Aleta R. Steevens, Jenna C. Glatzer, Courtney C. Kellogg, Walter C. Low, Peter A. Santi, Amy E. Kiernan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The transcription factor sex determining region Y-box 2 (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 mouse 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 24-48 h, reflecting the nonsensory-to-sensory switch observed by fate mapping. Early loss or gain of SOX2 function led 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.

Original languageEnglish (US)
Article numberdev170522
JournalDevelopment (Cambridge)
Volume146
Issue number13
DOIs
StatePublished - Jul 2019

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under award numbers F31DC015153 (A.R.S.) and RO1 DC009250 (A.E.K.), and a private donation from Bridget Sperl and John McCormick supported the development of the Neurog1−/− mice (P.A.S. and W.C.L.). Additional support was received from a grant to the Department of Ophthalmology at the University of Rochester from the foundation Research to Prevent Blindness (RPB). Deposited in PMC for release after 12 months.

Funding Information:
Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under award numbers F31DC015153 (A.R.S.) and RO1 DC009250 (A.E.K.), and a private donation from Bridget Sperl and John McCormick supported the development of the Neurog1-/- mice (P.A.S. and W.C.L.). Additional support was received from a grant to the Department of Ophthalmology at the University of Rochester from the foundation Research to Prevent Blindness (RPB). Deposited in PMC for release after 12 months.

Publisher Copyright:
© 2019. Published by The Company of Biologists Ltd.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • Cochlea
  • Inner ear
  • Mouse
  • Otocyst
  • SOX2
  • Sensory
  • Specification

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