ArticlePLoS genetics2019
Sox2 and FGF20 interact to regulate organ of Corti hair cell and supporting cell development in a spatially-graded manner.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- The Notch ligand Jagged1 plays a dual role in cochlear hair cell regeneration.Nature communications · 2025Article
- Fibroblast Growth Factors: Roles and Emerging Therapeutic Applications.Current drug targets · 2025Review
- Decoding FGF/FGFR Signaling: Insights into Biological Functions and Disease Relevance.Biomolecules · 2024Review
- Isolation and Comprehensive Analysis of Cochlear Tissue-Derived Small Extracellular Vesicles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- 3D reconstruction of the mouse cochlea from scRNA-seq data suggests morphogen-based principles in apex-to-base specification.Developmental cell · 2024Article
- A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2Journal of the Association for Research in Otolaryngology : JARO · 2024Article
- Advanced Omics Techniques for Understanding Cochlear Genome, Epigenome, and Transcriptome in Health and Disease.Biomolecules · 2023Review
- Stepwise fate conversion of supporting cells to sensory hair cells in the chick auditory epithelium.iScience · 2023Article
- FGF20 and PGM2 variants are associated with childhood asthma in family-based whole-genome sequencing studies.Human molecular genetics · 2023Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- Cochlear Development; New Tools and Approaches.Frontiers in cell and developmental biology · 2022Review
- Comparative assessment of Fgf's diverse roles in inner ear development: A zebrafish perspective.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Review
- Article
- FGF20-FGFR1 signaling through MAPK and PI3K controls sensory progenitor differentiation in the organ of Corti.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Article
- Single-Cell RNA Sequencing Analysis Reveals Greater Epithelial Ridge Cells Degeneration During Postnatal Development of Cochlea in Rats.Frontiers in cell and developmental biology · 2021Article
- The Fgf8 subfamily (Fgf8, Fgf17 and Fgf18) is required for closure of the embryonic ventral body wall.Development (Cambridge, England) · 2020Article
- Analysis of FGF20-regulated genes in organ of Corti progenitors by translating ribosome affinity purification.Developmental dynamics : an official publication of the American Association of Anatomists · 2020Article
- Developmental GAD2 Expression Reveals Progenitor-like Cells with Calcium Waves in Mammalian Crista Ampullaris.iScience · 2020Article
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Authors and funding
4 authors at 3 institutions in 3 countries.
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Abstract
The mouse organ of Corti, housed inside the cochlea, contains hair cells and supporting cells that transduce sound into electrical signals. These cells develop in two main steps: progenitor specification followed by differentiation. Fibroblast Growth Factor (FGF) signaling is important in this developmental pathway, as deletion of FGF receptor 1 (Fgfr1) or its ligand, Fgf20, leads to the loss of hair cells and supporting cells from the organ of Corti. However, whether FGF20-FGFR1 signaling is required during specification or differentiation, and how it interacts with the transcription factor Sox2, also important for hair cell and supporting cell development, has been a topic of debate. Here, we show that while FGF20-FGFR1 signaling functions during progenitor differentiation, FGFR1 has an FGF20-independent, Sox2-dependent role in specification. We also show that a combination of reduction in Sox2 expression and Fgf20 deletion recapitulates the Fgfr1-deletion phenotype. Furthermore, we uncovered a strong genetic interaction between Sox2 and Fgf20, especially in regulating the development of hair cells and supporting cells towards the basal end and the outer compartment of the cochlea. To explain this genetic interaction and its effects on the basal end of the cochlea, we provide evidence that decreased Sox2 expression delays specification, which begins at the apex of the cochlea and progresses towards the base, while Fgf20-deletion results in premature onset of differentiation, which begins near the base of the cochlea and progresses towards the apex. Thereby, Sox2 and Fgf20 interact to ensure that specification occurs before differentiation towards the cochlear base. These findings reveal an intricate developmental program regulating organ of Corti development along the basal-apical axis of the cochlea.
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