Retinoid-X receptor signalling in the developing spinal cord

Ludmila Solomin, Clas B. Johansson, Rolf H. Zetterström, Reid P. Bissonnette, Richard A. Heyman, Lars Olson, Urban Lendahl, Jonas Frisén and Thomas Perlmann ()
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Ludmila Solomin: The Ludwig Institute for Cancer Research, Stockholm Branch
Clas B. Johansson: Karolinska Institute
Rolf H. Zetterström: Karolinska Institute
Reid P. Bissonnette: Ligand Pharmaceuticals, 10275 Science Center Drive
Richard A. Heyman: Ligand Pharmaceuticals, 10275 Science Center Drive
Lars Olson: Karolinska Institute
Urban Lendahl: Karolinska Institute
Jonas Frisén: Karolinska Institute
Thomas Perlmann: The Ludwig Institute for Cancer Research, Stockholm Branch

Nature, 1998, vol. 395, issue 6700, 398-402

Abstract: 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.

Date: 1998
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DOI: 10.1038/26515

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