Molecular Identification of a Major Retinoic-Acid-Synthesizing Enzyme, a Retinaldehyde-Specific Dehydrogenase

Authors

  • Dayao Zhao,

    1. Program in Neuroscience, Harvard Medical School, Boston, USA
    2. Howard Hughes Medical Institute, Harvard Medical School and Brigham and Women's Hospital, Boston, USA
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  • Peter McCaffery,

    1. Department of Neurobiology, Harvard Medical School, Boston, USA
    2. E. K. Shriver Center, Waltham, USA
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  • Kathryn J. Ivins,

    1. McLean Hospital, Belmont, USA
    2. Department of Psychiatry, Harvard Medical School, Boston, USA
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  • Rachael L. Neve,

    1. Program in Neuroscience, Harvard Medical School, Boston, USA
    2. Department of Genetics, Harvard Medical School, Boston, USA
    3. McLean Hospital, Belmont, USA
    4. Department of Psychiatry, Harvard Medical School, Boston, USA
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  • Patrick Hogan,

    1. Department of Neurobiology, Harvard Medical School, Boston, USA
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  • William W. Chin,

    1. Howard Hughes Medical Institute, Harvard Medical School and Brigham and Women's Hospital, Boston, USA
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  • Ursula C. Dräger

    Corresponding author
    1. Program in Neuroscience, Harvard Medical School, Boston, USA
    2. Department of Neurobiology, Harvard Medical School, Boston, USA
    3. E. K. Shriver Center, Waltham, USA
    4. Department of Psychiatry, Harvard Medical School, Boston, USA
      U. C. Dräger, E. Kennedy Shriver Center, Division Developmental Neuroscience, 200 Trapelo Rd, Waltham MA 02254, USA
      Fax:+1 617 894 9968.
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  • Note. The novel nucleotide sequence data published here have been submitted to the EMBL nucleotide sequence data bank and are available under accession number x99273. D. Zhao and P. McCaffery contributed equally to this work.

U. C. Dräger, E. Kennedy Shriver Center, Division Developmental Neuroscience, 200 Trapelo Rd, Waltham MA 02254, USA
Fax:+1 617 894 9968.

Abstract

Retinoic acid, a developmental signal implicated in the formation of the neural axis, is present at high levels in the early embryonic trunk region, where it is synthesized by a novel dehydrogenase. Here we show that the same enzyme is inducible by retinoic acid in P19 teratocarcinoma cells, and we report the cloning from P19 cells of a cDNA encoding a novel dehydrogenase, named retinaldehyde dehydrogenase-2 (RALDH-2). Expression in COS cells shows RALDH-2 to be highly effective in oxidation of retinaldehyde, with no detectable activity on any other aldehyde tested. In situ hybridization histochemistry on the embryonic trunk reveales RALDH-2 mRNA both in mesoderm and neuroectoderm, with highest neuroectodermal expression in the ventral horn of the spinal cord at two restricted locations along the anteroposterior axis, presumably the subpopulation of motoneurons that innervate the limbs.

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