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

Research output: Contribution to journalArticle

Jingchen Chen, Monica Tambalo, Meyer Barembaum, Ramya Ranganathan, Marcos Simoes-Costa, Marianne E. Bronner, Andrea Streit

Original languageEnglish
Pages (from-to)1531-1543
JournalDevelopment (Cambridge): for advances in developmental biology and stem cells
Volume144
Issue number8
Early online date11 Apr 2017
DOIs
Accepted/In press24 Feb 2017
E-pub ahead of print11 Apr 2017
Published15 Apr 2017

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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.

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