Abstract
The vertebrate inner ear arises from a pool of progenitors with the potential to contribute to all the sense organs and cranial ganglia in the head. Here we explore the molecular mechanisms that control ear specification from these precursors. Using a multi-omics approach combined with loss-of-function experiments we identify a core transcriptional circuit that imparts ear identity, along with the first genome-wide characterization of non-coding elements that integrate this information. This analysis places the transcription factor Sox8 at the top of the ear determination network. Introducing Sox8 into cranial ectoderm not only converts non-ear cells into ear progenitors, but also activates the cellular programs for ear morphogenesis and neurogenesis. Thus, Sox8 has the unique ability to remodel transcriptional networks in the cranial ectoderm towards ear identity.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Text updated to clarify and explain data analysis and experimental design. Included additional data in supplementary figures: i) sections for enhancer characterisation and control/knock-down experiments, ii) comparison of Sox8-overexpression with otic reference data set, iii) TFBS analysis of enhancers