Pou4f3 Deficiency Obstructs the Subtype Differentiation of Vestibular Hair Cells

Qin Zhou1,2 · Yikang Huang1,2 · Wenli Ni1,2 · Mingchuan Feng1,2 · Lingjie Wu1,2 · Chuijin Lai1,2 · Yanping Zhang1,2 · Wenyan Li1,2,3 · Yan Chen1,2

1 ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China 

2 NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 200031, China 

3 The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China

Abstract

Vestibular hair cells (HCs) in the inner ear, crucial for balance and spatial orientation, are classified into type I and type II subtypes, but the mechanisms regulating their differentiation remain unclear. In this study, we examined the role of Pou4f3, an important transcription factor, in vestibular HC differentiation using Pou4f3DTR/DTR (deficient) and Pou4f3CreER/CreER (knockout) mouse models. In Pou4f3-deficient mice, the HC number decreased, and immature HCs failed to develop type I characteristics, indicating a developmental arrest. While type II HCs differentiated normally, Pou4f3 deficiency disrupted HC bundle formation and cell polarity. Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification. This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration.

Keywords

Inner ear; Development; Vestibular system; Auditory system; Pou4f3; Hair cell; Cell subtype; Cell differentiation

[SpringerLink]