title: Fgf-signaling-dependent Sox9a and Atoh1a regulate otic neural development in zebrafish.
abstract: Fibroblast growth factors (Fgfs) play important roles in developmental processes of the inner ear, including the ontogeny of the statoacoustic ganglia (SAG) and hair cells. However, the detailed genetic mechanism(s) underlying Fgf/Fgfr-dependent otic neural development remains elusive. Using conditional genetic approaches and inhibitory small molecules, we have revealed that Fgfr-PI3K/Akt signaling is mainly responsible for zebrafish SAG development and have determined that Sox9a and Atoh1a act downstream of Fgfr-Akt signaling to specify and/or maintain the otic neuron fate during the early segmentation stage. Sox9a and Atoh1a coregulate numerous downstream factors identified through our ChIP-seq analyses, including Tlx2 and Eya2. Fgfr-Erk1/2 signaling contributes to ultricular hair cell development during a critical period between 9 and 15 hours postfertilization. Our work reveals that a genetic network of the previously known sensory determinant Atoh1 and the neural crest determinant Sox9 plays critical roles in SAG development. These newly uncovered roles for Atoh1and Sox9 in zebrafish otic development may be relevant to study in other species.
authors.affiliation: The Education Ministry Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Education Ministry Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: The Education Ministry Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: The Education Ministry Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wu
authors.affiliation: The Education Ministry Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.affiliation: The Education Ministry Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Zhao
authors.affiliation: The Education Ministry Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Zuoyan
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: The Education Ministry Key Laboratory of Cell Proliferation and Differentiation and the State Key Laboratory of Bio-membrane and Membrane Bio-engineering, School of Life Sciences, Peking University, Beijing 100871, China doliu@pku.edu.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D007758:Ear, Inner / Q000196:embryology* / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005726:Ganglia, Parasympathetic / Q000196:embryology* / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D055758:SOX9 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: C514187:Atoh1a protein, zebrafish; D017468:Receptors, Fibroblast Growth Factor; D055758:SOX9 Transcription Factor; C504918:Sox9a protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins; D005346:Fibroblast Growth Factors
keywords: Fgf signaling; Fgfr-Erk1/2; Fgfr-PI3K/Akt; hair cells; statoacoustic ganglia