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

The vertebrate inner ear arises early in development from a thickened epithelium, the otic placode. Specification toward an otic fate requires diverse signals and complex transcriptional inputs that act sequentially and/or in parallel. To uncover and integrate novel genes with known molecular players in the gene regulatory network (GRN) underlying otic development, we have performed transcriptome analyses of the presumptive otic region at sequential early stages of commitment toward inner ear identity. Our results identify hundreds of genes enriched at specific developmental time points, revealing dynamic changes in gene expression as a function of time during the transition from progenitor to committed otic state. Initial functional analysis of selected enriched transcription factors demonstrates a genetic hierarchy amongst these genes underlying this critical transition. Our results not only characterize the otic transcriptome in unprecedented detail but also identify new links in the GRN responsible for development of the presumptive inner ear. Overall design: 3 different biological samples at various developmental stages (5-6 somite stage, 8-9 somite stage, 11-12 somite stage) are included. Two additional samples (a whole embryo at somite stage 3, and posterior pre-placodal region at Hamburger-Hamilton stage 6 (HH6)) are used as reference for different comparisons.