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TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti

Author

Listed:
  • Marina Kaiser

    (Hannover Medical School)

  • Timo H. Lüdtke

    (Hannover Medical School)

  • Lena Deuper

    (Hannover Medical School)

  • Carsten Rudat

    (Hannover Medical School)

  • Vincent M. Christoffels

    (Amsterdam University Medical Centers)

  • Andreas Kispert

    (Hannover Medical School)

  • Mark-Oliver Trowe

    (Hannover Medical School)

Abstract

The auditory function of the mammalian cochlea relies on two types of mechanosensory hair cells and various non-sensory supporting cells. Recent studies identified the transcription factors INSM1 and IKZF2 as regulators of outer hair cell (OHC) fate. However, the transcriptional regulation of the differentiation of inner hair cells (IHCs) and their associated inner supporting cells (ISCs) has remained enigmatic. Here, we show that the expression of the transcription factor TBX2 is restricted to IHCs and ISCs from the onset of differentiation until adulthood and examine its function using conditional deletion and misexpression approaches in the mouse. We demonstrate that TBX2 acts in prosensory progenitors as a patterning factor by specifying the inner compartment of the sensory epithelium that subsequently gives rise to IHCs and ISCs. Hair cell-specific inactivation or misexpression causes transdifferentiation of hair cells indicating a cell-autonomous function of TBX2 in inducing and maintaining IHC fate.

Suggested Citation

  • Marina Kaiser & Timo H. Lüdtke & Lena Deuper & Carsten Rudat & Vincent M. Christoffels & Andreas Kispert & Mark-Oliver Trowe, 2022. "TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35214-4
    DOI: 10.1038/s41467-022-35214-4
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    References listed on IDEAS

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    1. Lauren Chessum & Maggie S. Matern & Michael C. Kelly & Stuart L. Johnson & Yoko Ogawa & Beatrice Milon & Mark McMurray & Elizabeth C. Driver & Andrew Parker & Yang Song & Gemma Codner & Christopher T., 2018. "Helios is a key transcriptional regulator of outer hair cell maturation," Nature, Nature, vol. 563(7733), pages 696-700, November.
    2. Likhitha Kolla & Michael C. Kelly & Zoe F. Mann & Alejandro Anaya-Rocha & Kathryn Ellis & Abigail Lemons & Adam T. Palermo & Kathy S. So & Joseph C. Mays & Joshua Orvis & Joseph C. Burns & Ronna Hertz, 2020. "Characterization of the development of the mouse cochlear epithelium at the single cell level," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    3. Teerawat Wiwatpanit & Sarah M. Lorenzen & Jorge A. Cantú & Chuan Zhi Foo & Ann K. Hogan & Freddie Márquez & John C. Clancy & Matthew J. Schipma & Mary Ann Cheatham & Anne Duggan & Jaime García-Añovero, 2018. "Trans-differentiation of outer hair cells into inner hair cells in the absence of INSM1," Nature, Nature, vol. 563(7733), pages 691-695, November.
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