Investigation on normal and abnormal development of the organs originated from branchial arches, especially secondary palates

视黄酸（RA）是各种生物过程和正常胚胎发育的必需物质，但高浓度时具有致畸性。RA通过RA受体（RARs）介导其作用，但RARs在发育中的腭中的表达尚不清楚。在啮齿动物中，RA引起的主要畸形之一是腭裂（CP）。我们研究了RAR、b和g信使rna （mrna）的正常表达模式，以及全反式和13顺式RAs对RAR mrna和蛋白表达的影响。在正常腭中，我们检测到RARa（2.8、3.8kb）、RARb （3.3kb）和RARg (3.7kb) mrna。RARa和g mRNA的表达在GD13.5时没有明显的顺序变化，但RARb mRNA的表达增加。全反式RA剂量为100 mg/kg的妊娠小鼠可诱导94%的胎儿CP，其上颚RARb和g mRNA水平升高，但只有RARb蛋白上调。100mg/kg 13顺式RA诱导19%的胎儿CP， RARb和g mRNA水平升高，但RARb和g蛋白水平未升高。这些研究结果表明，RARb mRNA在胎儿上颚的诱导与RA治疗后全反式RA的组织浓度密切相关，RARb可能是RA诱导致畸最重要的候选分子之一。

Retinoic acid (RA) is mandatory for various biological processes and normal embryonic development, but is teratogenic at high concentrations. RA mediates its effects by RA receptors (RARs) , but the expression of RARs in the developing palate is still unclear. In rodents, one of the major malformations induced by RA is cleft palate (CP) . We investigated the normal expression patterns of RARa, b, and g messenger RNAs (mRNAs) and the effects of all-trans and 13-cis RAs on the expression of RAR mRNAs and proteins in fetal mouse secondary palates. In normal palates, we detected RARa (2.8,3.8kb) , RARb (3.3kb) and RARg (3.7kb) mRNAs.The expression of RARa and g mRNA did not show apparent sequential changes, but that of RARb mRNA increased at GD13.5. Treatment of pregnant mice with 100 mg/kg all-trans RA induced CP in 94% of the fetuses, and elevated RARb and g mRNA levels in their palates, but only RARb protein was up-regulated. Treatment with 100mg/kg 13-cis RA induced CP in 19% of the fetuses, elevated RARb and g mRNA levels, but did not elevate RARb and g proteins. These findings indicate that the induction of RARb mRNA in the fetal palate correlates well with the tissue concentration of all-trans RA after RA treatm ent and RARb may be one of the most influential candidate molecules for RA-induced teratogenesis.