School of Life Sciences, University of Sussex, Falmer, Brighton, UK.
Dev Dyn. 2012 Apr;241(4):741-58. doi: 10.1002/dvdy.23748. Epub 2012 Feb 14.
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.
内源性视黄酸在脊椎动物的正常发育中起着关键作用，但过量时会致畸。在小鼠中，通过口服灌胃或腹腔注射给予额外的视黄酸。在这里，我们评估了一种通过巧克力/糖丸给药的新型非侵入性系统。我们使用这种传递系统来研究视黄酸在调节成纤维细胞生长因子 Fgf3 表达中的作用，发现视黄酸处理的时间对其对 Fgf3 表达的影响至关重要。在 7.75 dpc 时给予递增剂量的视黄酸会导致耳囊中 Fgf3 的剂量依赖性下调，并导致后脑的空间表达发生变化。对发育中内耳的详细分析还揭示了随着视黄酸剂量的增加，Fgf3 表达的侧化与给药时间有关。我们讨论了这些数据如何影响当前的视黄酸对耳囊模式形成的模型。
