The effect of retinoic acid on the formation of cerebellar compartments

为了表明内源性类风湿性关节炎对小脑发育模式有任何影响，必须证明类风湿性关节炎存在于胚胎小脑中，并且类风湿性关节炎受体以模式方式表达。在这项研究中，我们使用一种敏感和特异的质谱技术来鉴定胚胎小脑中的RA。先前我们在胚胎小脑中发现了RA受体rxrα和rxrβ，但它们是弥漫性表达的，不局限于任何特定的细胞层或区域（未发表的观察结果）。一些研究小组研究了视黄酸受体在发育中的大脑中的分布（Ruberte et al., 1990,1993; Yamagata et al. 1994），然而，他们没有描述发育中的小脑中的表达。在这里，我们研究了已知与RA受体相互作用的核受体，鸡卵白蛋白上游转录因子（COUP-TF）的表达（Jonk等，1994；Qiu等，1994；Neuman等，1995；Da Silva等，1995；Brubaker等，1996；Tsai和Tsai， 1997）。COUP转录因子是同一超家族中的孤儿核受体，在大多数情况下，已知它们可以抑制RA的作用（Qiu, 1996）。它们与其他几种核受体形成异源二聚体，包括9-顺式RA结合RXR和甲状腺激素和维生素D受体。COUP-TF2（也称为COUP-TFbeta）表现出一种有趣的模式，它在矢状带中表达，与Millen等人（1995）描述的En2基因互补。结果暗示类风湿关节炎可能参与小脑室的形成。

In order to suggest that endogenous RA has any effect on the patterning of cerebellar development, it has to be shown that RA is present in the embryonic cerebellum and that RA receptors are expressed in a patterned fashion. In this study we use a sensitive and specific mass spectrometry technique to identify RA in the embryonic cerebellum. Previously we identified the RA receptors RXRalpha and RXRbeta in the embryonic cerebellum, but they are expressed diffusely and not localized to any specific cell layer or zone (unpublished observation). Several group have examined the distribution of retinoic acid receptors in the developing brain (Ruberte et al., 1990, 1993 ; Yamagata et al. 1994), however, they did not describe the expression in the developing cerebellum. Here we investigated the expression of a nuclear receptor known to interact with the RA receptors, the chick ovalbumin upstream transcription factors (COUP-TF) (Jonk et al., 1994 ; Qiu et al. 1994 ; Neuman et al. 1995 ; Da Silva et al., 1995 ; Brubaker et al., 1996 ; Tsai and Tsai, 1997). The COUP transcription factors are orphan nuclear receptors in the same superfamily, and in most cases they are known to suppress RA actions (Qiu, 1996). They form heterodimers with several other nuclear receptors, including the 9-cis RA binding RXR and the thyroid hormone and vitamin D receptors. COUP-TF2 (also called COUP-TFbeta) showed an interesting pattern in that it was expressed in sagittal bands complementary to the En2 gene described by Millen et al (1995). The result implies the possibility of RA involvement in the formation of compartments of the cerebellum.