Molecular identification of a major retinoic-acid-synthesizing enzyme, a retinaldehyde-specific dehydrogenase.
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 reveals 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.
Zhao
D
D
Program in Neuroscience, Harvard Medical School, Boston, USA.
McCaffery
P
P
Ivins
K J
KJ
Neve
R L
RL
Hogan
P
P
Chin
W W
WW
Dräger
U C
UC
D000375:Aging; D000445:Aldehyde Oxidoreductases / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D000818:Animals; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000201:enzymology / Q000254:growth & development; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017931:DNA Primers; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development; D004790:Enzyme Induction; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D017403:In Situ Hybridization; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D012160:Retina / Q000201:enzymology; D050697:Retinal Dehydrogenase; D018243:Teratocarcinoma; D013737:Testis / Q000201:enzymology; D014158:Transcription, Genetic; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016375:Antisense Elements (Genetics); D017931:DNA Primers; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase