Identification of RALDH-3, a novel retinaldehyde dehydrogenase, expressed in the ventral region of the retina.
In the developing retina, a retinoic acid (RA) gradient along the dorso-ventral axis is believed to be a prerequisite for the establishment of dorso-ventral asymmetry. This RA gradient is thought to result from the asymmetrical distribution of RA-generating aldehyde dehydrogenases along the dorso-ventral axis. Here, we identified a novel aldehyde dehydrogenase specifically expressed in the chick ventral retina, using restriction landmark cDNA scanning (RLCS). Since this molecule showed enzymatic activity to produce RA from retinaldehyde, we designated it retinaldehyde dehydrogenase 3 (RALDH-3). Structural similarity suggested that RALDH-3 is the orthologue of human aldehyde dehydrogenase 6. We also isolated RALDH-1 which is expressed in the chick dorsal retina and implicated in RA formation. Raldh-3 was preferentially expressed first in the surface ectoderm overlying the ventral portion of the prospective eye region and then in the ventral retina, earlier than Raldh-1 in chick and mouse embryos. High level expression of Raldh-3 was also observed in the nasal region. In addition, we found that Pax6 mutants are devoid of Raldh-3 expression. These results suggested that Raldh-3 is the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development, and also in the development of the olfactory system.
Suzuki
R
R
Division of Molecular Neurobiology, National Institute for Basic Biology, Department of Molecular Biomechanics, The Graduate University for Advanced Studies, 38 Nishigonaka, Myodaiji-cho, Okazaki, Japan.
Shintani
T
T
Sakuta
H
H
Kato
A
A
Ohkawara
T
T
Osumi
N
N
Noda
M
M
D000445:Aldehyde Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D012160:Retina / Q000196:embryology* / Q000201:enzymology*; D050697:Retinal Dehydrogenase; D012172:Retinaldehyde / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D005136:Eye Proteins; D018398:Homeodomain Proteins; D007527:Isoenzymes; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase; D012172:Retinaldehyde