Foxi3 is necessary for the induction of the chick otic placode in response to FGF signaling

Dev Biol. 2014 Jul 15;391(2):158-69. doi: 10.1016/j.ydbio.2014.04.014. Epub 2014 Apr 26.


Vertebrate cranial sensory organs are derived from region at the border of the anterior neural plate called the pre-placodal region (PPR). The otic placode, the anlagen of the inner ear, is induced from PPR ectoderm by FGF signaling. We have previously shown that competence of embryonic ectoderm to respond to FGF signaling during otic placode induction correlates with the expression of PPR genes, but the molecular basis of this competence is poorly understood. Here, we characterize the function of a transcription factor, Foxi3 that is expressed at very early stages in the non-neural ectoderm and later in the PPR of chick embryos. Ablation experiments showed that the underlying hypoblast is necessary for the initiation of Foxi3 expression. Mis-expression of Foxi3 was sufficient to induce markers of non-neural ectoderm such as Dlx5, and the PPR such as Six1 and Eya2. Electroporation of Dlx5, or Six1 together with Eya1 also induced Foxi3, suggesting direct or indirect positive regulation between non-neural ectoderm genes and PPR genes. Knockdown of Foxi3 in chick embryos prevented the induction of otic placode markers, and was able to prevent competent cranial ectoderm from expressing otic markers in response to FGF2. In contrast, Foxi3 expression alone was not sufficient to confer competence to respond to FGF on embryonic ectoderm. Our analysis of PPR and FGF-responsive genes after Foxi3 knockdown at gastrula stages suggests it is not necessary for the expression of PPR genes at these stages, nor for the transduction of FGF signals. The early expression but late requirement for Foxi3 in ear induction suggests it may have some of the properties associated with pioneer transcription factors.

Keywords: Competence; FGF; Foxi3; Induction; Otic placode; Pre-placodal region.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chick Embryo
  • Ear / embryology*
  • Ectoderm / embryology
  • Face / embryology
  • Fibroblast Growth Factors / metabolism*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gastrula / embryology*
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Maxillofacial Development
  • Morpholinos / genetics
  • Neural Plate / embryology
  • Signal Transduction


  • Forkhead Transcription Factors
  • Morpholinos
  • Fibroblast Growth Factors