ArticleDevelopmental biology2012
TFE2 and GATA3 enhance induction of POU4F3 and myosin VIIa positive cells in nonsensory cochlear epithelium by ATOH1.
Article in Developmental biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
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- FDA-Approved Tedizolid Phosphate Prevents Cisplatin-Induced Hearing Loss Without Decreasing Its Anti-tumor Effect.Journal of the Association for Research in Otolaryngology : JARO · 2024Article
- Hair Cell Regeneration: From Animals to Humans.Clinical and experimental otorhinolaryngology · 2024Review
- SoxC transcription factors shape the epigenetic landscape to establish competence for sensory differentiation in the mammalian organ of Corti.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Gata3 is required in late proneurosensory development for proper sensory cell formation and organization.Scientific reports · 2023Article
- Gata3 is Required in Late Proneurosensory Development for Proper Sensory Cell Formation and Organization.Research square · 2023Article
- Norrie disease protein is essential for cochlear hair cell maturation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells.Frontiers in cellular neuroscience · 2021Article
- TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae.Frontiers in cellular neuroscience · 2021Article
- Aldh inhibitor restores auditory function in a mouse model of human deafness.PLoS genetics · 2020Article
- Direct cellular reprogramming and inner ear regeneration.Expert opinion on biological therapy · 2019Review
- DNA methylation dynamics during embryonic development and postnatal maturation of the mouse auditory sensory epithelium.Scientific reports · 2018Article
- Article
- High-resolution transcriptional dissection of in vivo Atoh1-mediated hair cell conversion in mature cochleae identifies Isl1 as a co-reprogramming factor.PLoS genetics · 2018Article
- Computational analysis of mRNA expression profiling in the inner ear reveals candidate transcription factors associated with proliferation, differentiation, and deafness.Human genomics · 2018Article
- CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss.The Journal of experimental medicine · 2018Article
- Article
- Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells.Organogenesis · 2018Article
- Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cellsNeural regeneration research · 2017Article
- The Promoter and Multiple Enhancers of the pou4f3 Gene Regulate Expression in Inner Ear Hair Cells.Molecular neurobiology · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Transcription factors (TFs) can regulate different sets of genes to determine specific cell types by means of combinatorial codes. We previously identified closely-spaced TF binding motifs located 8.2-8.5 kb 5' to the ATG of the murine Pou4f3 gene, a gene required for late hair cell (HC) differentiation and survival. These motifs, 100% conserved among four mammalian species, include a cluster of E-boxes preferred by TCF3/ATOH1 heterodimers as well as motifs for GATA factors and SP1. We hypothesized that these factors might interact to regulate the Pou4f3 gene and possibly induce a HC phenotype in non-sensory cells of the cochlea. Cochlear sensory epithelium explants were prepared from postnatal day 1.5 transgenic mice in which expression of GFP is driven by 8.5 kb of Pou4f3 5' genomic DNA (Pou4f3/GFP). Electroporation was used to transfect cells of the greater epithelial ridge with multiple plasmids encoding human ATOH1 (hATOH1), hTCF3 (also known as E2A or TEF2), hGATA3, and hSP1. hATOH1 or hTCF3 alone induced Pou4f3/GFP cells but hGATA3 and hSP1 did not. hATOH1 but not hTCF3 induced conversion of greater epithelial ridge cells into Pou4f3/GFP and myosin VIIa double-positive cells. Transfection of hATOH1 in combination with hTCF3 or hGATA3 induced 2-3X more Pou4f3/GFP cells, and similarly enhanced Pou4f3/GFP and myosin VIIa double-positive cells, when compared to hATOH1 alone. Triple or quadruple TF combinations were generally not more effective than double TF combinations except in the middle turn, where co-transfection of hATOH1, hE2A, and hGATA3 was more effective than hATOH1 plus either hTCF3 or hGATA3. The results demonstrate that TFs can cooperate in regulation of the Pou4f3 gene and in the induction of at least one other element of a HC phenotype. Our data further indicate that combinations of TFs can be more effective than individual TFs in the inner ear.
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