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

维甲酸（RA）是各种生物过程和正常胚胎发育的必需品，但在高浓度下具有致畸性。RA通过RA受体（RARs）介导其作用，但RARs在发育中的腭中的表达仍不清楚。在啮齿类动物中，由RA引起的主要畸形之一是腭裂（CP）。我们研究了RARa、B和g信使RNA（mRNA）的正常表达模式以及全反式和13顺式RAs对胎鼠次级腭中RAR mRNA和蛋白表达的影响。在正常腭部组织中检测到RARa（2.8、3.8kb）、RARb（3.3kb）和RARg（3.7kb）mRNA，其中RARa和RARb mRNA的表达在GD13.5时无明显的时序性变化，而RARb mRNA的表达在GD13.5时明显增加。用100 mg/kg全反式RA处理妊娠小鼠，在94%的胎儿中诱导CP，并且在其腭部中升高RARb和g mRNA水平，但仅RARb蛋白上调。100 mg/kg 13-cis RA处理19%的胎儿可诱导CP，RARb和g mRNA水平升高，但不升高RARb和g蛋白。这些结果表明，RA处理后，RARb mRNA在胎儿腭的诱导与全反式RA的组织浓度相关，RARb可能是RA诱导致畸作用的最有影响力的候选分子之一。

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.