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PMID:18927155

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Citation

Spoorendonk, KM, Peterson-Maduro, J, Renn, J, Trowe, T, Kranenbarg, S, Winkler, C and Schulte-Merker, S (2008) Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton. Development 135:3765-74

Abstract

Retinoic acid (RA) plays important roles in diverse biological processes ranging from germ cell specification to limb patterning. RA ultimately exerts its effect in the nucleus, but how RA levels are being generated and maintained locally is less clear. Here, we have analyzed the zebrafish stocksteif mutant, which exhibits severe over-ossification of the entire vertebral column. stocksteif encodes cyp26b1, a cytochrome P450 member that metabolizes RA. The mutant is completely phenocopied by treating 4 dpf wild-type embryos with either RA or the pharmacological Cyp26 blocker R115866, thus identifying a previously unappreciated role for RA and cyp26b1 in osteogenesis of the vertebral column. Cyp26b1 is expressed within osteoblast cells, demonstrating that RA levels within these cells need to be tightly controlled. Furthermore, we have examined the effect of RA on osteoblasts in vivo. As numbers of osteoblasts do not change upon RA treatment, we suggest that RA causes increased activity of axial osteoblasts, ultimately resulting in defective skeletogenesis.

Links

PubMed Online version:10.1242/dev.024034

Keywords

Animals; Animals, Genetically Modified; Cytochrome P-450 Enzyme System/metabolism; Embryo, Nonmammalian/cytology; Embryo, Nonmammalian/embryology; Embryo, Nonmammalian/metabolism; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Mice; Mutation/genetics; Oryzias; Osteoblasts/cytology; Osteoblasts/drug effects; Osteoblasts/enzymology; Osteogenesis/drug effects; Phenotype; Transcription Factors/genetics; Transcription Factors/metabolism; Tretinoin/pharmacology; Zebrafish/embryology; Zebrafish/metabolism

Significance

Annotations

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

DANRE:CP26B

involved_in

GO:0030278: regulation of ossification

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-090415-1

P

Seeded From UniProt

complete

DANRE:CP26B

involved_in

GO:0034653: retinoic acid catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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