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

Author:

Chen Jingchen1,Tambalo Monica1,Barembaum Meyer2,Ranganathan Ramya1,Simões-Costa Marcos2,Bronner Marianne E.2,Streit Andrea1ORCID

Affiliation:

1. Department of Craniofacial Development and Stem Cell Biology, King's College London, London SE1 9RT, United Kingdom

2. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA

Abstract

The inner ear is a complex vertebrate sense organ, yet 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 program, the genes and genetic sub-circuits discovered here may be useful for reprogramming naïve cells towards otic identity to restore hearing loss.

Funder

Biotechnology and Biological Sciences Research Council

Action on Hearing Loss

National Institute on Deafness and Other Communication Disorders

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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