Retinoid signaling competence and RARβ‐mediated gene regulation in the developing mammalian telencephalon

Abstract

To study retinoid signaling in the developing telencephalon, we transfected a retinoid reporter gene into different regions of developing telencephalon. We found that the ventral telencephalon was more competent to retinoid signaling than the dorsal telencephalon. Moreover, among all retinoic acid receptors (RARs) and retinoid X receptors (RXRs), RAR␤ was strongly induced by retinoic acid in the ventral telencephalon, suggesting that RAR␤ might be involved in retinoid signaling competence. The RT-PCR analysis indicated that RAR␤ was selectively expressed in the developing striatum of ventral telencephalon. We then demonstrated that null mutations of RAR␤ gene resulted in reduction of striatal-enriched tyrosine phosphatase (STEP) mRNA in the striatum of RAR␤ Ϫ/Ϫ mutant mice. Conversely, the gain-of-function study showed that ectopic expression of RAR␤1 in the cerebral cortex enhanced STEP expression, and the effect was RAR␤-isoform specific. Our study identified RAR␤ as an important molecule for transducing retinoid signals in developing ventral telencephalon. Developmental Dynamics 232:887-900, 2005.

Modular patterning of structure and function of the striatum by retinoid receptor signaling

“…The cultivation of explant tissue, Sil-15 RA reporter cells, and ST14 cells was performed as described (9,20,23 …”

“…We further determined the endogenous RA level in the LGE with a coculture assay. Using the Sil-15 RA reporter cells, RA produced by explant tissue could be detected by activation of the ␤-galactosidase reporter gene (9,23). Few X-gal-positive cells were found when cocultured with E11.5 LGE (Fig.…”

“…A fundamentally interesting question is whether retinoids can pattern functional organization in the forebrain that generates cognitive behavior. Previous studies have shown that development of the intermediate part of telencephalon, which gives rise to the striatum in the mammalian telencephalon, is regulated by retinoid signaling (6)(7)(8)(9)(10). It is, however, unknown whether retinoid signaling is involved in control of compartmental formation during striatal development.…”

Genetic Patterning of the mammalian telencephalon by morphogenetic molecules and transcription factors

“…Moreover, Raldh1 (AHD2), another RA synthesizing enzyme, is present in axonal terminals of mesostriatal afferents that innervate the LGE/striatum (McCaffery and Drager, 1994). These findings suggest that the concentration of endogenous RA should be high in the LGE, which is confirmed by cocultures of telencepahlic explants with an RA reporter cell line showing that the LGE contains high levels of RA relative to other regions in the developing telencephalon (Toresson et al, 1999;Liao et al, 2005b). Radial glia have in fact been suggested to produce RA in the LGE (Toresson et al, 1999).…”

“…The enrichment of RA signaling molecules in the LGE therefore constitutes the specificity of RA signaling competence in the developing telencephalon. Indeed, the LGE cells are competent to RA signaling as shown by an RA reporter gene assay (Liao et al, 2005b). Moreover, the RA signaling competence may be mediated by RARb (Liao et al, 2005b), and ectopic expression of RARb1 in developing cerebral cortical cells induces expression of LGE/ striatal markers, including the dopamine signaling molecules of dopamine D1 receptor, dopamine and cyclic adenosine 3 0 :5 0 monophosphate-regulated phosphoprotein (DARPP-32), and striatal-enriched tyrosine (STEP) (Liao and Liu, 2005;Liao et al, 2005b).…”