ArticleDevelopment (Cambridge, England)2015
Neurog1 can partially substitute for Atoh1 function in hair cell differentiation and maintenance during organ of Corti development.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 36 citations in OpenAlex.
- Abnormal iron homeostasis mediates cochlear hair cell impairment and hearing loss in Gprasp2-deficient mice.Communications biology · 2026Article
- Regulatory Networks Driving the Specification, Differentiation, and Diversification of Neurons in the Mouse Inner Ear.Journal of the Association for Research in Otolaryngology : JARO · 2026Review
- Sponge bHLH Gene Expression inInternational journal of molecular sciences · 2025Article
- Irx3/5 Null Deletion in Mice Blocks Cochlea-Saccule Segregation and Disrupts the Auditory Tonotopic Map.The Journal of comparative neurology · 2024Article
- Genetic and pharmacologic alterations of claudin9 levels suffice to induce functional and mature inner hair cells.bioRxiv : the preprint server for biology · 2024Article
- The proper timing of Atoh1 expression is pivotal for hair cell subtype differentiation and the establishment of inner ear function.Cellular and molecular life sciences : CMLS · 2023Article
- Early Steps towards Hearing: Placodes and Sensory Development.International journal of molecular sciences · 2023Review
- Age-Related Hearing Loss: Sensory and Neural Etiology and Their Interdependence.Frontiers in aging neuroscience · 2022Review
- Development in the Mammalian Auditory System Depends on Transcription Factors.International journal of molecular sciences · 2021Review
- Near-infrared stimulation of the auditory nerve: A decade of progress toward an optical cochlear implant.Laryngoscope investigative otolaryngology · 2021Review
- Neurog1, Neurod1, and Atoh1 are essential for spiral ganglia, cochlear nuclei, and cochlear hair cell development.Faculty reviews · 2021Review
- Transcription factor Isl1 is dispensable for the development of the mouse prosensory region.Cytotechnology · 2020Article
- Using Sox2 to alleviate the hallmarks of age-related hearing loss.Ageing research reviews · 2020Review
- Knockdown of Foxg1 in supporting cells increases the trans-differentiation of supporting cells into hair cells in the neonatal mouse cochlea.Cellular and molecular life sciences : CMLS · 2020Article
- Tsukushi is essential for the development of the inner ear.Molecular brain · 2020Article
- Frizzled-9+ Supporting Cells Are Progenitors for the Generation of Hair Cells in the Postnatal Mouse Cochlea.Frontiers in molecular neuroscience · 2019Article
- A RNAscope whole mount approach that can be combined with immunofluorescence to quantify differential distribution of mRNA.Cell and tissue research · 2018Article
- Multichannel optrodes for photonic stimulation.Neurophotonics · 2018Article
- Understanding Molecular Evolution and Development of the Organ of Corti Can Provide Clues for Hearing Restoration.Integrative and comparative biology · 2018Article
- Pressure in the Cochlea During Infrared Irradiation.IEEE transactions on bio-medical engineering · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Atoh1, a basic helix-loop-helix (bHLH) transcription factor (TF), is essential for the differentiation of hair cells (HCs), mechanotransducers that convert sound into auditory signals in the mammalian organ of Corti (OC). Previous work demonstrated that replacing mouse Atoh1 with the fly ortholog atonal rescues HC differentiation, indicating functional replacement by other bHLH genes. However, replacing Atoh1 with Neurog1 resulted in reduced HC differentiation compared with transient Atoh1 expression in a 'self-terminating' Atoh1 conditional null mouse (Atoh1-Cre; Atoh1(f/f)). We now show that combining Neurog1 in one allele with removal of floxed Atoh1 in a self-terminating conditional mutant (Atoh1-Cre; Atoh1(f/kiNeurog1)) mouse results in significantly more differentiated inner HCs and outer HCs that have a prolonged longevity of 9 months compared with Atoh1 self-terminating littermates. Stereocilia bundles are partially disorganized, disoriented and not HC type specific. Replacement of Atoh1 with Neurog1 maintains limited expression of Pou4f3 and Barhl1 and rescues HCs quantitatively, but not qualitatively. OC patterning and supporting cell differentiation are also partially disrupted. Diffusible factors involved in patterning are reduced (Fgf8) and factors involved in cell-cell interactions are affected (Jag1, Hes5). Despite the presence of many HCs with stereocilia these mice are deaf, possibly owing to HC and OC patterning defects. This study provides a novel approach to disrupt OC development through modulating the HC-specific intracellular TF network. The resulting disorganized OC indicates that normally differentiated HCs act as 'self-organizers' for OC development and that Atoh1 plays a crucial role to initiate HC stereocilia differentiation independently of HC viability.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.