ArticlePloS one2010
RAF kinase activity regulates neuroepithelial cell proliferation and neuronal progenitor cell differentiation during early inner ear development.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- IGF-1 Controls Metabolic Homeostasis and Survival in HEI-OC1 Auditory Cells through AKT and mTOR Signaling.Antioxidants (Basel, Switzerland) · 2023Article
- Ceramide Kinase Inhibition Blocks IGF-1-Mediated Survival of Otic Neurosensory Progenitors by Impairing AKT Phosphorylation.Frontiers in cell and developmental biology · 2021Article
- Article
- Otic Neurogenesis Is Regulated by TGFβ in a Senescence-Independent Manner.Frontiers in cellular neuroscience · 2020Article
- TGFβ2-induced senescence during early inner ear development.Scientific reports · 2019Article
- Enhancement of neural stem cell survival, proliferation and differentiation by IGF-1 delivery in graphene oxide-incorporated PLGA electrospun nanofibrous mats.RSC advances · 2019Article
- Autophagy in the Vertebrate Inner Ear.Frontiers in cell and developmental biology · 2017Review
- Chemotherapeutic xCT inhibitors sorafenib and erastin unraveled with the synaptic optogenetic function analysis tool.Cell death discovery · 2017Article
- Insulin-like growth factor-1 improves diabetic cardiomyopathy through antioxidative and anti-inflammatory processes along with modulation of Akt/GSK-3β signaling in rats.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2016Article
- IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain.Frontiers in neuroscience · 2016Review
- C-Raf deficiency leads to hearing loss and increased noise susceptibility.Cellular and molecular life sciences : CMLS · 2015Article
- Application of insulin-like growth factor-1 in the treatment of inner ear disorders.Frontiers in pharmacology · 2014Review
- Knockdown of cyclin-dependent kinase 10 (cdk10) gene impairs neural progenitor survival via modulation of raf1a gene expression.The Journal of biological chemistry · 2013Article
- Article
- Early otic development depends on autophagy for apoptotic cell clearance and neural differentiation.Cell death & disease · 2012Article
- Autophagy during vertebrate development.Cells · 2012Article
- Insulin receptor substrate 2 (IRS2)-deficient mice show sensorineural hearing loss that is delayed by concomitant protein tyrosine phosphatase 1B (PTP1B) loss of function.Molecular medicine (Cambridge, Mass.) · 2012Article
- Article
- The molecular basis of making spiral ganglion neurons and connecting them to hair cells of the organ of Corti.Hearing research · 2011Review
- The role of insulin-like growth factor-I in the physiopathology of hearing.Frontiers in molecular neuroscience · 2011Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEarly inner ear development requires the strict regulation of cell proliferation, survival, migration and differentiation, coordinated by the concerted action of extrinsic and intrinsic factors. Deregulation of these processes is associated with embryonic malformations and deafness. We have shown that insulin-like growth factor I (IGF-I) plays a key role in embryonic and postnatal otic development by triggering the activation of intracellular lipid and protein kinases. RAF kinases are serine/threonine kinases that regulate the highly conserved RAS-RAF-MEK-ERK signaling cascade involved in transducing the signals from extracellular growth factors to the nucleus. However, the regulation of RAF kinase activity by growth factors during development is complex and still not fully understood. METHODOLOGY/PRINCIPAL
findingsBy using a combination of qRT-PCR, Western blotting, immunohistochemistry and in situ hybridization, we show that C-RAF and B-RAF are expressed during the early development of the chicken inner ear in specific spatiotemporal patterns. Moreover, later in development B-RAF expression is associated to hair cells in the sensory patches. Experiments in ex vivo cultures of otic vesicle explants demonstrate that the influence of IGF-I on proliferation but not survival depends on RAF kinase activating the MEK-ERK phosphorylation cascade. With the specific RAF inhibitor Sorafenib, we show that blocking RAF activity in organotypic cultures increases apoptosis and diminishes the rate of cell proliferation in the otic epithelia, as well as severely impairing neurogenesis of the acoustic-vestibular ganglion (AVG) and neuron maturation. CONCLUSIONS/SIGNIFICANCE: We conclude that RAF kinase activity is essential to establish the balance between cell proliferation and death in neuroepithelial otic precursors, and for otic neuron differentiation and axonal growth at the AVG.
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