title: Eya1 acts upstream of Tbx1, Neurogenin 1, NeuroD and the neurotrophins BDNF and NT-3 during inner ear development.
abstract: Cell fate specification during inner ear development is dependent upon regional gene expression within the otic vesicle. One of the earliest cell fate determination steps in this system is the specification of neural precursors, and regulators of this process include the Atonal-related basic helix-loop-helix genes, Ngn1 and NeuroD and the T-box gene, Tbx1. In this study we demonstrate that Eya1 signaling is critical to the normal expression patterns of Tbx1, Ngn1, and NeuroD in the developing mouse otocyst. We discuss a potential mechanism for the absence of neural precursors in the Eya1-/- inner ears and the primary and secondary mechanisms for the loss of cochleovestibular ganglion cells in the Eya1bor/bor hypomorphic mutant.
authors.affiliation: Gonda Department of Cell and Molecular Biology, House Ear Institute, 2100 W. Third Street, Los Angeles, CA 90057, USA. rfriedman@hei.org
authors.forename: Rick A
authors.initials: RA
authors.lastname: Friedman
authors.forename: Linna
authors.initials: L
authors.lastname: Makmura
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Biesiada
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Keithley
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016923:Cell Death; D019070:Cell Lineage; D003051:Cochlea / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D020933:Neurotrophin 3 / Q000096:biosynthesis / Q000502:physiology*; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes / Q000737:chemistry; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000502:physiology*; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019208:Brain-Derived Neurotrophic Factor; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D017027:Protein Tyrosine Phosphatases; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C491573:Tbx1 protein, mouse; C093564:Neurogenic differentiation factor 1; C486336:Neurog1 protein, mouse; C501156:Eya1 protein, mouse