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Updated: Jun 21, 2026

Zinc-finger Nuclease Enhanced Gene Targeting in Human Embryonic Stem Cells
Published on: August 23, 2014
The Pitx2c N-terminal domain is a critical interaction domain required for asymmetric morphogenesis
Annie Simard1, Luciano Di Giorgio, Melanie Amen
1The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
Abstract:
The paired-like homeodomain transcription factor Pitx2c has an essential role in patterning the left-right axis. However, neither its transcriptional targets nor the molecular mechanisms through which it exerts its patterning function are known. Here we provide evidence that the N-terminal domain of Pitx2c is important for this activity. Overexpression of the Pitx2c N-terminus in ovo randomizes the direction of heart looping, the first morphological asymmetry conserved in vertebrate embryos. In addition, the Pitx2c N-terminal domain blocks the ability of Pitx2c to synergize with Nkx2.5 to transactivate the procollagen lysyl hydroxylase (Plod-1) promoter in transient transfection assays. A five amino acid region containing leucine-41 is required for both of these effects. Our data suggest that the Pitx2c N-terminal domain competes with endogenous Pitx2c for binding to a protein interaction partner that is required for the activation of genes that direct asymmetric morphogenesis along the left-right axis.
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