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PMID:10588879

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Citation

Swindell, EC, Thaller, C, Sockanathan, S, Petkovich, M, Jessell, TM and Eichele, G (1999) Complementary domains of retinoic acid production and degradation in the early chick embryo. Dev. Biol. 216:282-96

Abstract

Excess retinoids as well as retinoid deprivation cause abnormal development, suggesting that retinoid homeostasis is critical for proper morphogenesis. RALDH-2 and CYP26, two key enzymes that carry out retinoic acid (RA) synthesis and degradation, respectively, were cloned from the chick and show significant homology with their orthologs in other vertebrates. Expression patterns of RALDH-2 and CYP26 genes were determined in the early chick embryo by in situ hybridization. During gastrulation and neurulation RALDH-2 and CYP26 were expressed in nonoverlapping regions, with RALDH-2 transcripts localized to the presumptive presomitic and lateral plate mesoderm and CYP26 mRNA to the presumptive mid- and forebrain. The two domains of expression were separated by an approximately 300-micrometer-wide gap, encompassing the presumptive hindbrain. In the limb region, a similar spatial segregation of RALDH-2 and CYP26 expression was found at stages 14 and 15. Limb region mesoderm expressed RALDH-2, whereas the overlying limb ectoderm expressed CYP26. RA-synthesizing and -degrading enzymatic activities were measured biochemically in regions expressing RALDH-2 or CYP26. Regions expressing RALDH-2 generated RA efficiently from precursor retinal but degraded RA only inefficiently. Conversely, tissue expressing CYP26 efficiently degraded but did not synthesize RA. Localized regions of RA synthesis and degradation mediated by these two enzymes may therefore provide a mechanism to regulate RA homeostasis spatially in vertebrate embryos.

Links

PubMed Online version:10.1006/dbio.1999.9487

Keywords

Aldehyde Oxidoreductases/genetics; Amino Acid Sequence; Animals; COS Cells; Chick Embryo; Cloning, Molecular; Cytochrome P-450 Enzyme System/genetics; Gene Expression Regulation, Developmental/drug effects; Gene Expression Regulation, Enzymologic/drug effects; In Situ Hybridization; Molecular Sequence Data; RNA, Messenger/metabolism; Retinal Dehydrogenase; Transfection; Tretinoin/metabolism; Tretinoin/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CP26A

acts_upstream_of_or_within

GO:0034653: retinoic acid catabolic process

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q9PUB4

P

Seeded From UniProt

complete

CHICK:CP26A

acts_upstream_of_or_within

GO:0034653: retinoic acid catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:CP26A

enables

GO:0008401: retinoic acid 4-hydroxylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CHICK:CP26A

involved_in

GO:0034653: retinoic acid catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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