Dynamic expression of retinoic acid-synthesizing and -metabolizing enzymes in the developing mouse inner ear

Raymond Romand, Takako Kondo, Valérie Fraulob, Martin Petkovich, Pascal Dollé, Eri Hashino

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Retinoic acid signaling plays essential roles in morphogenesis and neural development through transcriptional regulation of downstream target genes. It is believed that the balance between the activities of synthesizing and metabolizing enzymes determines the amount of active retinoic acid to which a developing tissue is exposed. In this study, we investigated spatiotemporal expression patterns of four synthesizing enzymes, the retinaldehyde dehydrogenases 1, 2, 3, and 4 (Raldh1, Raldh2, Raldh3, and Raldh4) and two metabolizing enzymes (Cyp26A1 and Cyp26B1) in the embryonic and postnatal mouse inner ear by using quantitative reverse transcriptase polymerase chain reaction (RT-PCR), in situ hybridization, and Western blot analysis. Quantitative RT-PCR analysis and Western blot data revealed that the expression of CYP26s was much higher than that of Raldhs at early embryonic ages but that Cyp26 expression was downregulated during embryonic development. Conversely, the expression levels of Raldh2 and -3 increased during development and were significantly higher than the Cyp26 levels at postnatal day 20. At this age, Raldh3 was expressed predominantly in the cochlea, whereas Raldh2 was present in the vestibular end organ. At early embryonic stages, as observed by in situ hybridization, the synthesizing enzymes were expressed only in the dorsoventral epithelium of the otocyst, whereas the metabolizing enzymes were present mainly in mesenchymal cells surrounding the otic epithelium. At later stages, Raldh2, Raldh3, and Cyp26B1 were confined to the stria vascularis, spiral ganglion, and supporting cells in the cochlear and vestibular epithelia, respectively. The downregulation of Cyp26s and the upregulation of Raldhs after birth during inner ear maturation suggest tissue changes in the sensitivity to retinoic acid concentrations.

Original languageEnglish
Pages (from-to)643-654
Number of pages12
JournalJournal of Comparative Neurology
Volume496
Issue number5
DOIs
StatePublished - Jun 10 2006

Fingerprint

Inner Ear
Tretinoin
Enzymes
Epithelium
Cochlea
Reverse Transcriptase Polymerase Chain Reaction
In Situ Hybridization
Down-Regulation
Western Blotting
Stria Vascularis
Retinaldehyde
Spiral Ganglion
Morphogenesis
Embryonic Development
Ear
Oxidoreductases
Up-Regulation
Parturition
Genes

Keywords

  • Cochlea
  • Cyp26a1
  • Cyp26b1
  • In situ hybridization
  • Raldh1
  • Raldh2
  • Raldh3
  • Raldh4
  • RT-PCR
  • Vestibular organ
  • Western blot

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Dynamic expression of retinoic acid-synthesizing and -metabolizing enzymes in the developing mouse inner ear. / Romand, Raymond; Kondo, Takako; Fraulob, Valérie; Petkovich, Martin; Dollé, Pascal; Hashino, Eri.

In: Journal of Comparative Neurology, Vol. 496, No. 5, 10.06.2006, p. 643-654.

Research output: Contribution to journalArticle

Romand, Raymond ; Kondo, Takako ; Fraulob, Valérie ; Petkovich, Martin ; Dollé, Pascal ; Hashino, Eri. / Dynamic expression of retinoic acid-synthesizing and -metabolizing enzymes in the developing mouse inner ear. In: Journal of Comparative Neurology. 2006 ; Vol. 496, No. 5. pp. 643-654.
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AU - Dollé, Pascal

AU - Hashino, Eri

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