Differential expression of genes encoding α, β and γ retinoic acid receptors and CRABP in the developing limbs of the mouse (original) (raw)

Nature volume 342, pages 702–705 (1989)Cite this article

Abstract

RETINOIC acid has profound effects on vertebrate limb morphogenesis (refs 1–6, reviewed in refs 7–9), including in the mouse, where it can act as a teratogen generating phocomelia and bone defects10–12. A retinoic acid gradient13–15, possibly amplified by a graded distribution of cellular retinoic acid-binding protein (CRABP) 16, could provide positional information across the antero-posterior axis of the chick limb bud. The discovery of nuclear retinoic acid receptors (RARs) 17–22 acting as retinoic acid-inducible enhancer factors (reviewed in refs 23,24) provided a basis for understanding how retinoic acid signals could be transduced at the level of gene expression25. We have now used in situ hybridization to study the distribution of messenger RNA transcripts of the three murine receptors (mRARs) and CRABP during mouse limb development. Both mRARo_α_ and mRAR_γ_ transcripts, but not those for mRAR_β_, are present and uniformly distributed in the limb bud at day 10 post-coitum, whereas CRABP transcripts have a graded proximo-distal distribution, indicating that differential expression of CRABP, but not of mRAR_α_ or mRAR_γ_, could participate in the establishment of the morphogenetic field. At later stages, mRAR_γ_ transcripts become specific to the cartilage cell lineage and to the differentiating skin and mRAR_β_ transcripts are mostly restricted to the interdigital mesenchyme. CRABP transcripts, however, are excluded from regions expressing mRAR_γ;_ and mRAR_β_. These results indicate that all three RARs and CRABP have specific functions during morphogenesis and differentiation of the mouse limb.

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Author notes

  1. Carol M. Stoner and Lorraine J. Gudas: Department of Biological Chemistry and Pharmacology, Harvard Medical School, and Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
  2. Pierre Chambon: To whom correspondence should be addressed.

Authors and Affiliations

  1. Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de I'lNSERM, Institut de Chimie Biologique, Faculté de médecine, 11 rue Humann, 67085, Strasbourg Cédex, France
    Pascal Dollé, Esther Ruberte, Philippe Kastner, Martin Petkovich, Carol M. Stoner, Lorraine J. Gudas & Pierre Chambon

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  1. Pascal Dollé
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  2. Esther Ruberte
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  3. Philippe Kastner
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  4. Martin Petkovich
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  5. Carol M. Stoner
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  6. Lorraine J. Gudas
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  7. Pierre Chambon
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Dollé, P., Ruberte, E., Kastner, P. et al. Differential expression of genes encoding α, β and γ retinoic acid receptors and CRABP in the developing limbs of the mouse.Nature 342, 702–705 (1989). https://doi.org/10.1038/342702a0

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