Retinoic acid-metabolizing enzyme Cyp26a1 is essential for determining territories of hindbrain and spinal cord in zebrafish

Retinoic acid-metabolizing enzyme Cyp26a1 is essential for determining territories of hindbrain... Retinoic acid (RA) plays a critical role in neural patterning and organogenesis in the vertebrate embryo. Here we characterize a mutant of the zebrafish named giraffe ( gir ) in which the gene for the RA-degrading enzyme Cyp26a1 is mutated. The gir mutant displayed patterning defects in multiple organs including the common cardinal vein, pectoral fin, tail, hindbrain, and spinal cord. Analyses of molecular markers suggested that the lateral plate mesoderm is posteriorized in the gir mutant, which is likely to cause the defects of the common cardinal vein and pectoral fin. The cyp26a1 expression in the rostral spinal cord was strongly upregulated in the gir mutant, suggesting a strong feedback control of its expression by RA signaling. We also found that the rostral spinal cord territory was expanded at the expense of the hindbrain territory in the gir mutant. Such a phenotype is the opposite of that of the mutant for Raldh2, an enzyme that synthesizes RA. We propose a model in which Cyp26a1 attenuates RA signaling in the prospective rostral spinal cord to limit the expression of hox genes and to determine the hindbrain–spinal cord boundary. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Developmental Biology Elsevier

Retinoic acid-metabolizing enzyme Cyp26a1 is essential for determining territories of hindbrain and spinal cord in zebrafish

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Publisher
Elsevier
Copyright
Copyright © 2004 Elsevier Inc.
ISSN
0012-1606
eISSN
1095-564X
D.O.I.
10.1016/j.ydbio.2004.11.023
Publisher site
See Article on Publisher Site

Abstract

Retinoic acid (RA) plays a critical role in neural patterning and organogenesis in the vertebrate embryo. Here we characterize a mutant of the zebrafish named giraffe ( gir ) in which the gene for the RA-degrading enzyme Cyp26a1 is mutated. The gir mutant displayed patterning defects in multiple organs including the common cardinal vein, pectoral fin, tail, hindbrain, and spinal cord. Analyses of molecular markers suggested that the lateral plate mesoderm is posteriorized in the gir mutant, which is likely to cause the defects of the common cardinal vein and pectoral fin. The cyp26a1 expression in the rostral spinal cord was strongly upregulated in the gir mutant, suggesting a strong feedback control of its expression by RA signaling. We also found that the rostral spinal cord territory was expanded at the expense of the hindbrain territory in the gir mutant. Such a phenotype is the opposite of that of the mutant for Raldh2, an enzyme that synthesizes RA. We propose a model in which Cyp26a1 attenuates RA signaling in the prospective rostral spinal cord to limit the expression of hox genes and to determine the hindbrain–spinal cord boundary.

Journal

Developmental BiologyElsevier

Published: Feb 15, 2005

References

  • Beyond the neckless phenotype: influence of reduced retinoic acid signaling on motor neuron development in the zebrafish hindbrain
    Begemann, G.; Marx, M.; Mebus, K.; Meyer, A.; Bastmeyer, M.
  • Endogenous retinoids in the zebrafish embryo and adult
    Costaridis, P.; Horton, C.; Zeitlinger, J.; Holder, N.; Maden, M.
  • Metabolic inactivation of retinoic acid by a novel P450 differentially expressed in developing mouse embryos
    Fujii, H.; Sato, T.; Kaneko, S.; Gotoh, O.; Fujii-Kuriyama, Y.; Osawa, K.; Kato, S.; Hamada, H.
  • Endogenous distribution of retinoids during normal development and teratogenesis in the mouse embryo
    Horton, C.; Maden, M.
  • Independent roles for retinoic acid in segmentation and neuronal differentiation in the zebrafish hindbrain
    Linville, A.; Ergi Gumusaneli, E.; Chandraratna, R.A.S.; Schilling, T.F.
  • A second CYP26 P450 in humans and zebrafish: CYP26B1
    Nelson, D.R.
  • Retinoids regulate the anterior expression boundaries of 5' Hoxb genes in posterior hindbrain
    Oosterveen, T.; Niederreither, K.; Dolle, P.; Chambon, P.; Meijlink, F.; Deschamps, J.
  • Retinoic acid-mediated gene expression in transgenic reporter zebrafish
    Perz-Edwards, A.; Hardison, N.L.; Linney, E.
  • Retinoic acid is required for the initiation of outgrowth in the chick limb bud
    Stratford, T.; Horton, C.; Maden, M.
  • Complementary domains of retinoic acid production and degradation in the early chick embryo
    Swindell, E.C.; Thaller, C.; Sockanathan, S.; Petkovich, M.; Jessell, T.M.; Eichele, G.
  • Vitamin A deficiency results in the dose-dependent acquisition of anterior character and shortening of the caudal hindbrain of the rat embryo
    White, J.C.; Highland, M.; Kaiser, M.; Clagett-Dame, M.

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