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PMID:17164423

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Citation

Hernandez, RE, Putzke, AP, Myers, JP, Margaretha, L and Moens, CB (2007) Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development. Development 134:177-87

Abstract

Retinoic acid (RA) is essential for normal vertebrate development, including the patterning of the central nervous system. During early embryogenesis, RA is produced in the trunk mesoderm through the metabolism of vitamin A derived from the maternal diet and behaves as a morphogen in the developing hindbrain where it specifies nested domains of Hox gene expression. The loss of endogenous sources of RA can be rescued by treatment with a uniform concentration of exogenous RA, indicating that domains of RA responsiveness can be shaped by mechanisms other than the simple diffusion of RA from a localized posterior source. Here, we show that the cytochrome p450 enzymes of the Cyp26 class, which metabolize RA into polar derivatives, function redundantly to shape RA-dependent gene-expression domains during hindbrain development. In zebrafish embryos depleted of the orthologs of the three mammalian CYP26 genes CYP26A1, CYP26B1 and CYP26C1, the entire hindbrain expresses RA-responsive genes that are normally restricted to nested domains in the posterior hindbrain. Furthermore, we show that Cyp26 enzymes are essential for exogenous RA to rescue hindbrain patterning in RA-depleted embryos. We present a ;gradient-free' model for hindbrain patterning in which differential RA responsiveness along the hindbrain anterior-posterior axis is shaped primarily by the dynamic expression of RA-degrading enzymes.

Links

PubMed PMC1765950 Online version:10.1242/dev.02706

Keywords

Animals; Body Patterning/physiology; Cytochrome P-450 Enzyme System/genetics; Cytochrome P-450 Enzyme System/metabolism; Embryo, Nonmammalian; Embryonic Development/drug effects; Gene Expression Regulation, Developmental/drug effects; Genes, Homeobox; In Situ Hybridization; Models, Biological; Oligonucleotides, Antisense/pharmacology; Organogenesis; Rhombencephalon/drug effects; Rhombencephalon/embryology; Rhombencephalon/metabolism; Tretinoin/metabolism; Tretinoin/pharmacology; Zebrafish/embryology; Zebrafish/genetics; Zebrafish/metabolism

Significance

Annotations

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

DANRE:A1L1M2

involved_in

GO:0030902: hindbrain development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:A1L1M2

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:A1L1M2

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:CP26A

involved_in

GO:0030902: hindbrain development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:CP26A

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1

P

Seeded From UniProt

complete

DANRE:CP26A

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:CP26A

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:CP26A

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2

P

Seeded From UniProt

complete

DANRE:CP26A

involved_in

GO:0042573: retinoic acid metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2

P

Seeded From UniProt

complete

DANRE:CP26A

involved_in

GO:0042574: retinal metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2

P

Seeded From UniProt

complete

DANRE:Q4G283

involved_in

GO:0030902: hindbrain development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:Q4G283

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:Q4G283

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:Q508U6

involved_in

GO:0030902: hindbrain development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:Q508U6

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:Q508U6

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:CP26B

involved_in

GO:0030902: hindbrain development

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

DANRE:CP26B

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1

P

Seeded From UniProt

complete

DANRE:CP26B

involved_in

GO:0021661: rhombomere 4 morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

ZFIN:ZDB-GENO-070411-2,ZFIN:ZDB-MRPHLNO-070410-1,ZFIN:ZDB-MRPHLNO-070410-6

P

Seeded From UniProt

complete

See also

References

See Help:References for how to manage references in GONUTS.