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Retinoid-X receptor signalling in the developing spinal cord

Nature volume 395, pages 398–402 (1998)Cite this article

Abstract

Retinoids regulate gene expression through the action of retinoic acid receptors (RARs) and retinoid-X receptors (RXRs), which both belong to the family of nuclear hormone receptors1,2. Retinoids are of fundamental importance during development2, but it has been difficult to assess the distribution of ligand-activated receptors in vivo. This is particularly the case for RXR, which is a critical unliganded auxiliary protein for several nuclear receptors, including RAR1, but its ligand-activated role in vivo remains uncertain. Here we describe an assay in transgenic mice, based on the expression of an effector fusion protein linking the ligand-binding domain of either RXR or RAR to the yeast Gal4 DNA-binding domain, and the in situ detection of ligand-activated effector proteins by using an inducible transgenic lacZ reporter gene. We detect receptor activation in the spinal cord in a pattern that indicates that the receptor functions in the maturation of limb-innervating motor neurons. Our results reveal a specific activation pattern of Gal4–RXR which indicates that RXR is a critical bona fide receptor in the developing spinal cord.

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Figure 1: Transgenic effector–reporter assay.
Figure 2: Induction of β-galactosidase expression in transgenic mice.
Figure 3: Spatiotemporal shift of β-galactosidase-positive cells in the developing spinal cord.
Figure 4: Induction and inhibition of β-galactosidase expression in E10.5 spinal cord explant cultures of gRXR/lacZr transgenic embryos.

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Acknowledgements

We thank S. Sockanathan, T. Jessell and P. Chambon for communicating unpublished results and for discussion; T. Jessell and P. Ljungdahl for Islet-1 and HA antibodies; A.Mata for transfections; E. Nilsson, K. Jansson, Karin Lundströmer and E. Lindqvist for technical support; L. Foley for SR11237; and R. Pettersson for comments. This work was supported by the Swedish Medical Research Council, and the US Public Health Service.

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Authors and Affiliations

  1. The Ludwig Institute for Cancer Research, Stockholm Branch, PO Box 240, S-171 77, Stockholm, Sweden

    Ludmila Solomin & Thomas Perlmann

  2. Departments of Cell and Molecular Biology, Karolinska Institute, S-171 77, Stockholm, Sweden

    Clas B. Johansson, Urban Lendahl & Jonas Frisén

  3. Departments of Neuroscience, Karolinska Institute, S-171 77, Stockholm, Sweden

    Rolf H. Zetterström & Lars Olson

  4. Ligand Pharmaceuticals, 10275 Science Center Drive, San Diego, 92121, California, USA

    Reid P. Bissonnette & Richard A. Heyman

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Correspondence to Thomas Perlmann.

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Solomin, L., Johansson, C., Zetterström, R. et al. Retinoid-X receptor signalling in the developing spinal cord. Nature 395, 398–402 (1998). https://doi.org/10.1038/26515

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