Retinoid-X receptor signalling in the developing spinal cord

Nature. 1998 Sep 24;395(6700):398-402. doi: 10.1038/26515.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Culture Techniques
  • Extremities / embryology
  • Extremities / innervation
  • Genes, Reporter
  • Humans
  • Mice
  • Mice, Transgenic
  • Motor Neurons / physiology
  • Receptors, Retinoic Acid / metabolism*
  • Retinoid X Receptors
  • Signal Transduction*
  • Spinal Cord / embryology*
  • Spinal Cord / metabolism
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • beta-Galactosidase

Substances

  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Transcription Factors
  • beta-Galactosidase