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

Development. 2017 Apr 15;144(8):1531-1543. doi: 10.1242/dev.148494. Epub 2017 Mar 6.

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.

Keywords: Auditory system; Cell fate; Chick; Embryo; Hearing; Placode; Transcription factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chick Embryo
  • Cluster Analysis
  • Ear, Inner / embryology*
  • Ear, Inner / metabolism*
  • Feedback, Physiological
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks*
  • Models, Biological
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Systems Biology / methods*
  • Time Factors
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • RNA, Messenger
  • Transcription Factors