The effect of retinoic acid on the formation of cerebellar compartments

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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in the embryonic cerebellum, but they are expressed diffusely and not localized to any specific cell layer or zone (unpublished observation).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.