A novel method for retinoic acid administration reveals differential and dose-dependent downregulation of Fgf3 in the developing inner ear and anterior CNS.

Endogenous retinoic acid plays critical roles in normal vertebrate development, but can be teratogenic in excess. In mice, additional retinoic acid is administered by oral gavage or intraperitoneal injection. Here we evaluate a novel non-invasive system for administering retinoic acid via chocolate/sugar pellets. We use this delivery system to examine the role of retinoic acid in regulating the expression of the fibroblast growth factor Fgf3, and find that the timing of retinoic acid treatment is critical for its effects on Fgf3 expression. Administration of increasing amounts of retinoic acid at 7.75 dpc leads to dose-dependent downregulation of Fgf3 in the otocyst and changes in spatial expression in the hindbrain. Detailed analysis of the developing inner ear also reveals a lateralisation of Fgf3 expression with increasing retinoic acid dose that is dependent on timing of administration. We discuss how these data impact on current models of retinoic acid patterning of the otocyst.