title: Zebrafish Foxi1 provides a neuronal ground state during inner ear induction preceding the Dlx3b/4b-regulated sensory lineage.
abstract: Vertebrate inner ear development is a complex process that involves the induction of a common territory for otic and epibranchial precursors and their subsequent segregation into otic and epibranchial cell fates. In zebrafish, the otic-epibranchial progenitor domain (OEPD) is induced by Fgf signaling in a Foxi1- and Dlx3b/4b-dependent manner, but the functional differences of Foxi1 and Dlx3b/4b in subsequent cell fate specifications within the developing inner ear are poorly understood. Based on pioneer tracking (PioTrack), a novel Cre-dependent genetic lineage tracing method, and genetic data, we show that the competence to embark on a neuronal or sensory fate is provided sequentially and very early during otic placode induction. Loss of Foxi1 prevents neuronal precursor formation without affecting hair cell specification, whereas loss of Dlx3b/4b inhibits hair cell but not neuronal precursor formation. Consistently, in Dlx3b/4b- and Sox9a-deficient b380 mutants almost all otic epithelial fates are absent, including sensory hair cells, and the remaining otic cells adopt a neuronal fate. Furthermore, the progenitors of the anterior lateral line ganglia also arise from the OEPD in a Foxi1-dependent manner but are unaffected in the absence of Dlx3b/4b or in b380 mutants. Thus, in addition to otic fate Foxi1 provides neuronal competence during OEPD induction prior to and independently of the Dlx3b/4b-mediated sensory fate of the developing inner ear.
authors.affiliation: Technische Universität Dresden, Biotechnology Center and DFG-Center for Regenerative Therapies Dresden Cluster of Excellence, Tatzberg 47-49, Dresden, Germany. stefan.hans@biotec.tu-dresden.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Hans
authors.forename: Anne
authors.initials: A
authors.lastname: Irmscher
authors.forename: Michael
authors.initials: M
authors.lastname: Brand
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage; D007758:Ear, Inner / Q000196:embryology* / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006198:Hair Cells, Auditory / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D060172:Morpholinos / Q000008:administration & dosage; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism* / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D060172:Morpholinos; D051762:PAX2 Transcription Factor; D055758:SOX9 Transcription Factor; C504918:Sox9a protein, zebrafish; D029961:Zebrafish Proteins; C498152:dlx3b protein, zebrafish; C472802:foxi1 protein, zebrafish; C497320:pax2a protein, zebrafish