Cochlear inner hair cells (IHCs) and outer hair cells (OHCs) require different transcription factors for their cell fate stabilization and survival, suggesting separate mechanisms are involved. Here, we found that the transcription factor Casz1 was crucial for early IHC fate consolidation and for OHC survival during mouse development. Loss of Casz1 resulted in transdifferentiation of IHCs into OHCs, without affecting OHC production. However, long-term OHC survival was compromised in mutant mice. In addition, the transcription factor Gata3 was down-regulated in -deleted IHCs and overexpressing Gata3 partially rescued IHC properties, OHC numbers, and hearing in -deleted mice. Thus, Casz1 plays critical roles in early IHC fate stabilization and OHC survival and could potentially provide a lead for therapies aimed at regenerating both IHCs and OHCs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/science.ado4930 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Casz1 is required for both inner hair cell fate stabilization and outer hair cell survival.
Science
January 2025
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Cochlear inner hair cells (IHCs) and outer hair cells (OHCs) require different transcription factors for their cell fate stabilization and survival, suggesting separate mechanisms are involved. Here, we found that the transcription factor Casz1 was crucial for early IHC fate consolidation and for OHC survival during mouse development. Loss of Casz1 resulted in transdifferentiation of IHCs into OHCs, without affecting OHC production.
View Article and Find Full Text PDFUndocking of an extensive ciliary network induces proteostasis and cell fate switching resulting in severe primary ciliary dyskinesia.
Sci Transl Med
January 2025
Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Article Synopsis
- Primary ciliary dyskinesia (PCD) is a rare genetic disorder linked to chronic respiratory issues, infertility, and problems with body asymmetry, primarily caused by mutations in the CCDC39 and CCDC40 genes.
- Researchers used advanced techniques to investigate how these genetic variants impact cellular functions beyond just causing cilia to stop moving.
- They discovered that the absence of CCDC39/CCDC40 creates a significant loss of over 90 ciliary structural proteins, leading to cilia dysfunction and other cellular issues, suggesting that gene therapy could potentially offer a new treatment strategy for PCD.
Distribution and Biological Response of Nanoplastics in Constructed Wetland Microcosms: Mechanistic Insights into the Role of Photoaging.
Environ Sci Technol
January 2025
Stockbridge School of Agriculture, University of Massachusetts, Amherst, Massachusetts 01003, United States.
Concern over nanoplastic contamination of wetland ecosystems has been increasing. However, little is known about the effect of photoaging on the distribution and biological response of the nanoplastics. Here, palladium-labeled polystyrene nanoplastics (PS-Pd NPs) at 0.
View Article and Find Full Text PDFActl6a regulates autophagy via Sox2-dependent Atg5 and Atg7 expression to inhibit apoptosis in spinal cord injury.
J Adv Res
January 2025
the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China. Electronic address:
Introduction: Spinal cord injury (SCI) is a severe central nervous system disorder with limited treatment options. While autophagy plays a protective role in neural repair, its regulatory mechanisms in SCI remain unclear. Actin-like protein 6A (Actl6a) influences cell fate and neural development, yet its specific role in SCI repair is not well understood.
View Article and Find Full Text PDFPrognosis of Implant-Based Breast Reconstruction After Mastectomy Flap Necrosis: Predictors of Failure and Salvage.
Aesthetic Plast Surg
January 2025
Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Background: In the realm of implant-based breast reconstruction, mastectomy flap necrosis (MFN) is a prevalent yet grave complication that poses a threat to the stability of the inserted prosthesis. Although numerous investigations have scrutinized the risk factors for MFN development, few have delved into the aftermath, specifically implant failure or salvage. This study seeks to appraise the prognosis of the implanted prosthesis following MFN occurrence, as well as identify predictors of such outcomes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!