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Dispensable role of Rac1 and Rac3 after cochlear hair cell specification.

Takashi Nakamura1,2, Hirofumi Sakaguchi2, Hiroaki Mohri1

  • 1Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe, 657-8501, Japan.

Journal of Molecular Medicine (Berlin, Germany)
|May 19, 2023
PubMed
Summary
This summary is machine-generated.

Rac small GTPases are not essential for mature cochlear hair cells or hearing. Deleting Rac1 and Rac3 after hair cell specification in mice did not affect hearing or hair cell structure.

Keywords:
Atoh1DevelopmentHearingMaintenanceRho-family small GTPases

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Neuroscience

Background:

  • Rac small GTPases are crucial for embryonic inner ear development.
  • Their specific roles in cochlear hair cells post-specification remain largely unknown.

Purpose of the Study:

  • To investigate the function and activation of Rac small GTPases in cochlear hair cells after their specification.
  • To determine the necessity of Rac1 and Rac3 for hair cell maturation and hearing maintenance.

Main Methods:

  • Utilized GFP-tagged Rac plasmids and a Rac1-FRET biosensor mouse model.
  • Generated Rac1-knockout and Rac1/Rac3-double knockout mice using the Atoh1 promoter for cell-specific deletion.
  • Assessed cochlear hair cell morphology and hearing function at various ages, including after noise exposure.

Main Results:

  • Rac1 and Rac3 deletion after hair cell specification did not impact cochlear hair cell morphology at 13 weeks or hearing function at 24 weeks.
  • Rac1/Rac3-double knockout mice showed no hearing vulnerability after intense noise exposure at 6 weeks.
  • Atoh1 promoter activity was confirmed post-embryonic day 14, coinciding with hair cell precursor cell cycle exit.

Conclusions:

  • Rac1 and Rac3 are dispensable for the maturation of cochlear hair cells in the postmitotic state.
  • These GTPases are not required for maintaining hearing function after hair cell maturation.
  • While important for early development, Rac1 and Rac3 are not critical for established cochlear function.