Transforming growth factor-β1 signaling participates in the physiological and pathological regulation of mouse inner ear development by all-trans retinoic acid
✍ Scribed by Sydney C. Butts; Wei Liu; Geming Li; Dorothy A. Frenz
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 481 KB
- Volume
- 73
- Category
- Article
- ISSN
- 1542-0752
No coin nor oath required. For personal study only.
✦ Synopsis
BACKGROUND: Retinoic acid (RA) is a vitamin A derivative that participates in patterning and regulation of inner ear development. Either excess RA or RA deficiency during a critical stage of inner ear development can produce teratogenic effects. Previous studies have shown that in utero exposure of the developing mouse inner ear to a high dose of all-trans RA (atRA) results in severe malformations of the inner ear that are associated with diminished levels of endogenous transforming growth factor-1 (TGF- 1 ) protein. METHODS: In this study, the effects of a teratogenic level of atRA on levels and patterns of expression of TGF receptor II (TGFRII) and Smad2, a downstream component of the TGF signal transduction pathway, are investigated in the developing mouse inner ear. The expression pattern of endogenous RA receptor ␣ (RAR␣) and the ability of an RAR␣ 1specific antisense oligonucleotide (AS) to modulate otic capsule chondrogenesis are demonstrated in the inner ear and in culture. RESULTS: Endogenous TGFRII and Smad2 are downregulated in the inner ear following in utero atRA treatment. In addition, a reduction in endogenous TGF 1 and a marked suppression of chondrogenesis occur in RAR␣ 1 AS-treated cultures in comparison to untreated or oligonucleotide-treated control cultures. This chondrogenic suppression can be partially overcome by supplementation of RAR␣ 1 AS-treated cultures with exogenous TGF 1 protein. CONCLUSIONS: Our findings support a role for TGF in the physiological and pathological effects of RA on inner ear development.