PUBLICATION

Identification of RNA binding motif proteins essential for cardiovascular development

Authors
Maragh, S., Miller, R.A., Bessling, S.L., McGaughey, D.M., Wessels, M.W., de Graaf, B., Stone, E.A., Bertoli-Avella, A.M., Gearhart, J.D., Fisher, S., and McCallion, A.S.
ID
ZDB-PUB-111027-38
Date
2011
Source
BMC Developmental Biology   11(1): 62 (Journal)
Registered Authors
Fisher, Shannon, McCallion, Andy, Stone, Eric
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Binding Sites
  • Cardiovascular System/embryology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental*
  • Morphogenesis/genetics
  • RNA/metabolism
  • RNA-Binding Proteins/genetics*
  • RNA-Binding Proteins/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
22011202 Full text @ BMC Dev. Biol.
Abstract

Background

We recently identified Rbm24 as a novel gene expressed during mouse cardiac development. Due to its tightly restricted and persistent expression from formation of the cardiac crescent onwards and later in forming vasculature we posited it to be a key player in cardiogenesis with additional roles in vasculogenesis and angiogenesis.

Results

To determine the role of this gene in cardiac development, we have identified its zebrafish orthologs (rbm24a and rbm24b), and functionally evaluated them during zebrafish embryogenesis. Consistent with our underlying hypothesis, reduction in expression of either ortholog through injection of morpholino antisense oligonucleotides results in cardiogenic defects including cardiac looping and reduced circulation, leading to increasing pericardial edema over time. Additionally, morphant embryos for either ortholog display incompletely overlapping defects in the forming vasculature of the dorsal aorta (DA), posterior caudal vein (PCV) and caudal vein (CV) which are the first blood vessels to form in the embryo. Vasculogenesis and early angiogenesis in the trunk were similarly compromised in rbm24 morphant embryos at 48 hours post fertilization (hpf). Subsequent vascular maintenance was impaired in both rbm24 morphants with substantial vessel degradation noted at 72 hpf.

Conclusion

Taken collectively, our functional data support the hypothesis that rbm24a and rbm24b are key developmental cardiac genes with unequal roles in cardiovascular formation.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping