Molecular Signaling in Retinoic Acid-Induced Inner Ear Teratogenesis

Garritano, Frank G.; Frenz, Dorothy A.

doi:10.4137/cment.s1116

Cited by 2 publications

(4 citation statements)

References 84 publications

(134 reference statements)

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“…This perturbation in hindbrain development at E7.75–E8 correlates with inner ear defects, and presumably reflects indirect effects of RA on the developing inner ear. However, maternal administration of RA subsequent to hindbrain patterning, at E9, impacts on patterning and morphogenesis of the inner ear putatively due to direct affects of RA [Frenz and Liu, 2000; Garritano and Frenz, 2008].…”

Section: What Basic Principles Underlie Inner Ear Development That Mamentioning

confidence: 99%

“…2) [Glover et al, 2006; Romand et al, 2006]. However, the expression of the RA synthetic enzymes (Raldh1, Raldh2, and Raldh3) and RA receptors (RARα and RARβ) within the otic epithelium itself [Romand et al, 2006, 2002] supports the contention that RA synthesized in the otic epithelium may act directly and locally on this tissue to control gene expression and thus regulate some aspects of its normal development [Garritano and Frenz, 2008]. Furthermore, since RARα, β, and particularly γ are expressed in periotic mesenchyme, RA synthesized by the Raldh enzymes in the otic epithelium may act by diffusion on the surrounding mesenchyme to influence inner ear development [Romand et al, 2006] by means of a reciprocal interaction.…”

Section: How Does Ra Influence the Developing Inner Ear?—direct Versumentioning

confidence: 99%

“…RA signaling is likely to mediate its effects by modulating other signaling pathways that regulate inner ear development [Garritano and Frenz, 2008]. The FGFs comprise a family of signaling molecules that regulate cell proliferation, differentiation, and migration during embryogenesis [Ornitz and Itoh, 2001] and are essential for appropriate patterning and formation of the developing inner ear [Alvarez et al, 2003; Wright and Mansour, 2003].…”

Section: Molecular Mechanisms Of Teratogenicity—what Signaling Pathwamentioning

confidence: 99%

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Retinoid signaling in inner ear development: A “Goldilocks” phenomenon

Frenz

Liu

Cvekl

et al. 2010

American J of Med Genetics Pt A

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Retinoic acid is a biologically active derivative of vitamin A that is indispensable for inner ear development. The normal function of retinoic acid is achieved only at optimal homeostatic concentrations, with an excess or deficiency in retinoic acid leading to inner ear dysmorphogenesis. We present an overview of the role of retinoic acid in the developing mammalian inner ear, discussing both how and when retinoic acid may act to critically control a program of inner ear development. Molecular mechanisms of otic teratogenicity involving two members of the fibroblast growth factor family, FGF3 and FGF10, and their downstream targets, Dlx5 and Dlx6, are examined under conditions of both retinoic acid excess and deficiency. We term the effect of too little or too much retinoic acid on FGF/Dlx signaling a Goldilocks phenomenon. We demonstrate that in each case (retinoic acid excess, retinoic acid deficiency), retinoic acid can directly affect FGF3/FGF10 signaling within the otic epithelium, leading to downregulated expression of these essential signaling molecules, which in turn, leads to diminution in Dlx5/Dlx6 expression. Non-cell autonomous affects of the otic epithelium subsequently occur, altering transforming growth factor beta (TGFβ) expression in the neighboring periotic mesenchyme and serving as a putative explanation for retinoic acid-mediated otic capsule defects. We conclude that retinoic acid coordinates inner ear morphogenesis by controlling an FGF/Dlx signaling cascade, whose perturbation by deviations in local retinoid concentrations can lead to inner ear dysmorphogenesis.

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Section: What Basic Principles Underlie Inner Ear Development That Mamentioning

confidence: 99%

Section: How Does Ra Influence the Developing Inner Ear?—direct Versumentioning

confidence: 99%

Section: Molecular Mechanisms Of Teratogenicity—what Signaling Pathwamentioning

confidence: 99%

See 1 more Smart Citation

Retinoid signaling in inner ear development: A “Goldilocks” phenomenon

Frenz

Liu

Cvekl

et al. 2010

American J of Med Genetics Pt A

Self Cite

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show abstract

Section: Molecular Mechanisms Of Teratogenicity—what Signaling Pathwamentioning

confidence: 99%

Morphology change of biaxially oriented polytetrafluoroethylene membranes caused by solvent soakage

Wang¹,

Tang²,

Li³

et al. 2011

J of Applied Polymer Sci

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The morphological changes of expanded polytetrafluoroethylene (ePTFE) membrane caused by solvent soakage were investigated in this study. The results demonstrated that the wettable solvent with low contact angle towards PTFE membrane can introduce huge stress to the ePTFE membrane and make the membrane shrinkage, and the stress is generated in the solvent evaporation procedure. The pore size and membrane dimension shrinkage of ePTFE membrane improved with the decrease of the solvent contact angle and surface tension. , the membrane thickness shrinkness are 15.0% and 16.7%, respectively. The evaporation-induced stress towards the ePTFE membrane also increases with the decrease of the solvent contact angle to the ePTFE membrane.

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Molecular Signaling in Retinoic Acid-Induced Inner Ear Teratogenesis

Cited by 2 publications

References 84 publications

Retinoid signaling in inner ear development: A “Goldilocks” phenomenon

Retinoid signaling in inner ear development: A “Goldilocks” phenomenon

Morphology change of biaxially oriented polytetrafluoroethylene membranes caused by solvent soakage

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