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A systems level approach reveals new gene regulatory modules in the developing ear

Chen, Jingchen and Tambalo, Monica and Barembaum, Meyer and Ranganathan, Ramya and Simões-Costa, Marcos and Bronner, Marianne E. and Streit, Andrea (2017) A systems level approach reveals new gene regulatory modules in the developing ear. Development, 144 (8). pp. 1531-1543. ISSN 0950-1991. PMCID PMC5399671. https://resolver.caltech.edu/CaltechAUTHORS:20170313-142540623

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/ 10.1242/dev.148494DOIArticle
http://dev.biologists.org/content/144/8/1531PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399671/PubMed CentralArticle
ORCID:
AuthorORCID
Bronner, Marianne E.0000-0003-4274-1862
Streit, Andrea0000-0001-7664-7917
Additional Information:© 2017 Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Received December 20, 2016; Accepted February 24, 2017. Funding: This study was funded by grants from the Biotechnology and Biological Sciences Research Council (BB/I021647/1), Deafness Research UK (513:KCL:AS) and the National Institute on Deafness and Other Communication Disorders (DC011577). Deposited in PMC for immediate release. Author contributions: A.S. designed the experiments; J.C. and M.T. collected otic tissues; R.R. performed RNAseq for PPR tissue; J.C. analysed RNAseq data; J.C. and M.T. performed most functional experiments and analysed all data together with A.S.; M.B. contributed to the knockdown experiments; M.S.-C. contributed to RNAseq experiments; J.C., A.S. and M.E.B. wrote the manuscript. Competing interests: The authors declare no competing or financial interests. Data availability: All sequencing data have been deposited in Gene Expression Omnibus under accession number GSE69185 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69185).
Funders:
Funding AgencyGrant Number
Biotechnology and Biological Sciences Research Council (BBSRC)BB/I021647/1
Deafness Research (UK)513:KCL:AS
NIHDC011577
Subject Keywords:auditory system, cell fate, chick, embryo, hearing, placode, transcription factor
Issue or Number:8
PubMed Central ID:PMC5399671
Record Number:CaltechAUTHORS:20170313-142540623
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170313-142540623
Official Citation:A systems-level approach reveals new gene regulatory modules in the developing ear Jingchen Chen, Monica Tambalo, Meyer Barembaum, Ramya Ranganathan, Marcos Simões-Costa, Marianne E. Bronner, Andrea Streit Development 2017 144: 1531-1543; doi: 10.1242/dev.148494
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75070
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:15 Mar 2017 18:52
Last Modified:03 Oct 2019 16:46

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