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

Dev Biol. 2005 Feb 15;278(2):415-27. doi: 10.1016/j.ydbio.2004.11.023.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Body Patterning / genetics
  • Chromosome Mapping
  • Cytochrome P-450 Enzyme System / metabolism*
  • DNA Primers
  • In Situ Hybridization
  • Morphogenesis
  • Mutation
  • Phenotype
  • Retinoic Acid 4-Hydroxylase
  • Rhombencephalon / embryology*
  • Rhombencephalon / enzymology
  • Spinal Cord / embryology*
  • Spinal Cord / enzymology
  • Tretinoin / metabolism*
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish Proteins


  • DNA Primers
  • Zebrafish Proteins
  • Tretinoin
  • Cytochrome P-450 Enzyme System
  • Retinoic Acid 4-Hydroxylase
  • cyp26a1 protein, zebrafish