title: A systems-level approach reveals new gene regulatory modules in the developing ear.
abstract: The inner ear is a complex vertebrate sense organ, yet it arises from a simple epithelium, the otic placode. Specification towards otic fate requires diverse signals and transcriptional inputs that act sequentially and/or in parallel. Using the chick embryo, we uncover novel genes in the gene regulatory network underlying otic commitment and reveal dynamic changes in gene expression. Functional analysis of selected transcription factors reveals the genetic hierarchy underlying the transition from progenitor to committed precursor, integrating known and novel molecular players. Our results not only characterize the otic transcriptome in unprecedented detail, but also identify new gene interactions responsible for inner ear development and for the segregation of the otic lineage from epibranchial progenitors. By recapitulating the embryonic programme, the genes and genetic sub-circuits discovered here might be useful for reprogramming naïve cells towards otic identity to restore hearing loss.
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: Jingchen
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: Monica
authors.initials: M
authors.lastname: Tambalo
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Meyer
authors.initials: M
authors.lastname: Barembaum
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, UK.
authors.forename: Ramya
authors.initials: R
authors.lastname: Ranganathan
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Marcos
authors.initials: M
authors.lastname: Simões-Costa
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Bronner
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, UK andrea.streit@kcl.ac.uk.
authors.forename: Andrea
authors.identifier: 0000-0001-7664-7917
authors.initials: A
authors.lastname: Streit
mesh_terms: D000818:Animals; D002642:Chick Embryo; D016000:Cluster Analysis; D007758:Ear, Inner / Q000196:embryology* / Q000378:metabolism*; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D014157:Transcription Factors
keywords: Auditory system; Cell fate; Chick; Embryo; Hearing; Placode; Transcription factor