Retinoid-X receptor signalling in the developing spinal cord.
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 receptors. Retinoids are of fundamental importance during development, 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 RAR, 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.
The Ludwig Institute for Cancer Research, Stockholm Branch, Sweden.
L
L
Solomin
C B
CB
Johansson
R H
RH
Zetterström
R P
RP
Bissonnette
R A
RA
Heyman
L
L
Olson
U
U
Lendahl
J
J
Frisén
T
T
Perlmann
D000818:Animals; D046508:Culture Techniques; D005121:Extremities / Q000196:embryology / Q000294:innervation; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase
D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D001616:beta-Galactosidase