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The Pitx2c N-Terminal Domain Is a Critical Interaction Domain Required for Asymmetric Morphogenesis
Journal article   Open access   Peer reviewed

The Pitx2c N-Terminal Domain Is a Critical Interaction Domain Required for Asymmetric Morphogenesis

Annie Simard, Luciano Di Giorgio, Melanie Amen, Ashley Westwood, Brad A. Amendt and Aimee K. Ryan
Developmental dynamics, Vol.238(10), pp.2459-2470
10/01/2009
DOI: 10.1002/dvdy.22062
PMCID: PMC3014603
PMID: 19681163
url
https://doi.org/10.1002/dvdy.22062View
Published (Version of record) Open Access

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. Developmental Dynamics 238.2459-2470, 2009. (c) 2009 Wiley-Liss, Inc.
Anatomy & Morphology Developmental Biology Life Sciences & Biomedicine Science & Technology

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