PUBLICATION

Cyp26 enzymes are required to balance the cardiac and vascular lineages within the anterior lateral plate mesoderm

Authors
Rydeen, A.B., Waxman, J.S.
ID
ZDB-PUB-140513-276
Date
2014
Source
Development (Cambridge, England)   141: 1638-48 (Journal)
Registered Authors
Waxman, Joshua
Keywords
Cardiovascular, Cyp26, Lateral plate mesoderm, Retinoic acid, Zebrafish
MeSH Terms
  • Animals
  • Biomarkers/metabolism
  • Blood Vessels/cytology*
  • Cell Count
  • Cell Differentiation/drug effects
  • Cell Lineage*/drug effects
  • Cytochrome P-450 Enzyme System/deficiency
  • Cytochrome P-450 Enzyme System/metabolism*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/enzymology
  • Endothelial Cells/cytology
  • Endothelial Cells/drug effects
  • Heart Atria/cytology
  • Mesoderm/blood supply
  • Mesoderm/cytology*
  • Mesoderm/drug effects
  • Mesoderm/enzymology*
  • Myocardium/cytology*
  • Skull/blood supply
  • Skull/drug effects
  • Skull/embryology
  • Stem Cells/cytology
  • Stem Cells/metabolism
  • Tretinoin/pharmacology
  • Zebrafish
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/metabolism*
(all 28)
PubMed
24667328 Full text @ Development
Abstract
Normal heart development requires appropriate levels of retinoic acid (RA) signaling. RA levels in embryos are dampened by Cyp26 enzymes, which metabolize RA into easily degraded derivatives. Loss of Cyp26 function in humans is associated with numerous developmental syndromes that include cardiovascular defects. Although previous studies have shown that Cyp26-deficient vertebrate models also have cardiovascular defects, the mechanisms underlying these defects are not understood. Here, we found that in zebrafish, two Cyp26 enzymes, Cyp26a1 and Cyp26c1, are expressed in the anterior lateral plate mesoderm (ALPM) and predominantly overlap with vascular progenitors (VPs). Although singular knockdown of Cyp26a1 or Cyp26c1 does not overtly affect cardiovascular development, double Cyp26a1 and Cyp26c1 (referred to here as Cyp26)-deficient embryos have increased atrial cells and reduced cranial vasculature cells. Examining the ALPM using lineage tracing indicated that in Cyp26-deficient embryos the myocardial progenitor field contains excess atrial progenitors and is shifted anteriorly into a region that normally solely gives rise to VPs. Although Cyp26 expression partially overlaps with VPs in the ALPM, we found that Cyp26 enzymes largely act cell non-autonomously to promote appropriate cardiovascular development. Our results suggest that localized expression of Cyp26 enzymes cell non-autonomously defines the boundaries between the cardiac and VP fields within the ALPM through regulating RA levels, which ensures a proper balance of myocardial and endothelial lineages. Our study provides novel insight into the earliest consequences of Cyp26 deficiency that underlie cardiovascular malformations in vertebrate embryos.
Genes / Markers
Figures
Figure Gallery (20 images) / 2
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ci1TgTransgenic Insertion
    ci5TgTransgenic Insertion
      f2TgTransgenic Insertion
        fb7TgTransgenic Insertion
          rw716
            Point Mutation
            sk72TgTransgenic Insertion
              ubs1TgTransgenic Insertion
                1 - 7 of 7
                Show
                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                Target Reagent Reagent Type
                cyp26a1MO4-cyp26a1MRPHLNO
                cyp26a1MO5-cyp26a1MRPHLNO
                cyp26c1MO1-cyp26c1MRPHLNO
                cyp26c1MO2-cyp26c1MRPHLNO
                tp53MO4-tp53MRPHLNO
                1 - 5 of 5
                Show
                Fish
                Antibodies
                Orthology
                No data available
                Engineered Foreign Genes
                Marker Marker Type Name
                DsRed2EFGDsRed2
                EGFPEFGEGFP
                mCherryEFGmCherry
                ZsYellowEFGZsYellow
                1 - 4 of 4
                Show
                Mapping
                No data available