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ZIRC
ZFIN ID: ZDB-PUB-090123-18
Nkx2.7 and Nkx2.5 function redundantly and are required for cardiac morphogenesis of zebrafish embryos
Tu, C.T., Yang, T.C., and Tsai, H.J.
Date: 2009
Source: PLoS One 4(1): e4249 (Journal)
Registered Authors: Tsai, Huai-Jen
Keywords: Embryos, Heart, Cardiac ventricles, Zebrafish, Cardiac atria, Hyperexpression techniques, Heart development, Morphogenesis
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Cell Proliferation
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins/chemistry
  • Heart/embryology*
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/physiology*
  • Myocardium/metabolism
  • Myocardium/pathology
  • Phenotype
  • T-Box Domain Proteins/physiology
  • Time Factors
  • Transcription Factors/genetics
  • Transcription Factors/physiology*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 19158954 Full text @ PLoS One
FIGURES
ABSTRACT
BACKGROUND: Nkx2.7 is the tinman-related gene, as well as orthologs of Nkx2.5 and Nkx-2.3. Nkx2.7 and Nkx2.5 express in zebrafish heart fields of lateral plate mesoderm. The temporal and spatial expression patterns of Nkx2.7 are similar to those of Nkx2.5, but their functions during cardiogenesis remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, Nkx2.7 is demonstrated to compensate for Nkx2.5 loss of function and play a predominant role in the lateral development of the heart, including normal cardiac looping and chamber formation. Knocking down Nkx2.5 showed that heart development was normal from 24 to 72 hpf. However, when knocking down either Nkx2.7 or Nkx2.5 together with Nkx2.7, it appeared that the heart failed to undergo looping and showed defective chambers, although embryos developed normally before the early heart tube stage. Decreased ventricular myocardium proliferation and defective myocardial differentiation appeared to result from late-stage up-regulation of bmp4, versican, tbx5 and tbx20, which were all expressed normally in hearts at an early stage. We also found that tbx5 and tbx20 were modulated by Nkx2.7 through the heart maturation stage because an inducible overexpression of Nkx2.7 in the heart caused down-regulation of tbx5 and tbx20. Although heart defects were induced by overexpression of an injection of 150-pg Nkx2.5 or 5-pg Nkx2.7 mRNA, either Nkx2.5 or Nkx2.7 mRNA rescued the defects induced by Nkx2.7-morpholino(MO) and Nkx2.5-MO with Nkx2.7-MO. CONCLUSIONS AND SIGNIFICANCE: Therefore, we conclude that redundant activities of Nkx2.5 and Nkx2.7 are required for cardiac morphogenesis, but that Nkx2.7 plays a more critical function, specifically indicated by the gain-of-function and loss-of- function experiments where Nkx2.7 is observed to regulate the expressions of tbx5 and tbx20 through the maturation stage.
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