ZFIN ID: ZDB-PUB-061227-41
Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development
Hernandez, R.E., Putzke, A.P., Myers, J.P., Margaretha, L., and Moens, C.B.
Date: 2007
Source: Development (Cambridge, England) 134(1): 177-187 (Journal)
Registered Authors: Hernandez, Rafael, Moens, Cecilia, Myers, Jonathan, Putzke, Aaron
Keywords: Retinoic acid, Hindbrain, Cyp26, Hox, Morphogen, Zebrafish
MeSH Terms:
  • 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
PubMed: 17164423 Full text @ Development
FIGURES
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.
ADDITIONAL INFORMATIONNo data available