Identification of cis-element regulating expression of the mouse Fgf10 gene during inner ear development

Hideyo Ohuchi, Akihiro Yasue, Katsuhiko Ono, Shunsuke Sasaoka, Sayuri Tomonari, Akira Takagi, Mitsuo Itakura, Keiji Moriyama, Sumihare Noji, Tsutomu Nohno

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45 Citations (Scopus)

Abstract

Fibroblast growth factor (FGF) signaling is crucial for the induction and growth of the ear, a sensory organ that involves intimate tissue interactions. Here, we report the abnormality of Fgf10 null ear and the identification of a cis-regulatory element directing otic expression of Fgf10. In Fgf10 null inner ears, we found that the initial development of semicircular, vestibular, and cochlear divisions is roughly normal, after which there are abnormalities of semicircular canal/cristae and vestibular development. The mutant semicircular disks remain without canal formation by the perinatal stage. To elucidate regulation of the Fgf10 expression during inner ear development, we isolated a 6.6-kb fragment of its 5′-upstream region and examined its transcriptional activity with transgenic mice, using a lacZ-reporter system. From comparison of the mouse sequences of the 6.6-kb fragment with corresponding sequences of the human and chicken Fgf10, we identified a 0.4-kb enhancer sequence that drives Fgf10 expression in the developing inner ear. The enhancer sequences have motifs for many homeodomain-containing proteins (e.g., Prx, Hox, Nkx), in addition to POU-domain factors (e.g., Brn3), zinc-finger transcription factors (e.g., GATA-binding factors), TCF/LEF-1, and a SMAD-interacting protein. Thus, FGF10 signaling is dispensable for specification of otic compartment identity but is required for hollowing the semicircular disk. Furthermore, the analysis of a putative inner ear enhancer of Fgf10 has disclosed a complicated regulation of Fgf1 during inner ear development by numerous transcription factors and signaling pathways.

Original languageEnglish
Pages (from-to)177-187
Number of pages11
JournalDevelopmental Dynamics
Volume233
Issue number1
DOIs
Publication statusPublished - May 2005

Keywords

  • Chicken genome
  • Enhancer analysis
  • Fgf10
  • Fgf10 knockout mouse
  • Inner ear development, semicircular canals
  • Mouse genome
  • Transgenic mouse
  • cis-element

ASJC Scopus subject areas

  • Developmental Biology

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    Ohuchi, H., Yasue, A., Ono, K., Sasaoka, S., Tomonari, S., Takagi, A., Itakura, M., Moriyama, K., Noji, S., & Nohno, T. (2005). Identification of cis-element regulating expression of the mouse Fgf10 gene during inner ear development. Developmental Dynamics, 233(1), 177-187. https://doi.org/10.1002/dvdy.20319