title: Jag1b is essential for patterning inner ear sensory cristae by regulating anterior morphogenetic tissue separation and preventing posterior cell death.
abstract: The sensory patches of the vertebrate inner ear, which contain hair cells and supporting cells, are essential for hearing and balance functions. How the stereotypically organized sensory patches are formed remains to be determined. In this study, we isolated a zebrafish mutant in which the jag1b gene is disrupted by an EGFP insertion. Loss of Jag1b causes cell death in the developing posterior crista and results in downregulation of fgf10a in the posterior prosensory cells. Inhibition of FGFR activity in wild-type embryos also causes loss of the posterior crista, suggesting that Fgf10a mediates Jag1b activity. By contrast, in the anterior prosensory domain, Jag1b regulates separation of a single morphogenetic field into anterior and lateral cristae by flattening cells destined to form a nonsensory epithelium between the two cristae. MAPK activation in the nonsensory epithelium precursors is required for the separation. In the jag1b mutant, MAPK activation and cell flattening are extended to anterior crista primordia, causing loss of anterior crista. More importantly, inhibition of MAPK activity, which blocks the differentiation of nonsensory epithelial cells, generated a fused large crista and extra hair cells. Thus, Jag1b uses two distinct mechanisms to form three sensory cristae in zebrafish.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Wei-Rui
authors.initials: WR
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China jianzhang84@genetics.ac.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D007758:Ear, Inner / Q000196:embryology* / Q000378:metabolism*; D051526:Fibroblast Growth Factor 10; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D002135:Calcium-Binding Proteins; D051526:Fibroblast Growth Factor 10; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D029961:Zebrafish Proteins; C520413:fgf10a protein, zebrafish
keywords: Cell death; Cristae; FGF; Inner ear; Jag1b; Notch; Zebrafish