Figure 6. Model of Pitx2-dependent regulation of gene expression.

Pitx2 is proposed to regulate genes that are activated in an isoform-independent manner (shown on the left in blue) and genes that are isoform-dependent (shown in red in middle panel). Left-right patterning genes in the lateral plate mesoderm are proposed to be dependent on the Pitx2c isoform. Our model proposes that activation of genes important for left-right patterning requires interaction between the Pitx2c N-terminal domain and other transcription factors (purple molecule in middle diagram) either directly as shown or via an intermediate. Our data showed that these interactions can be blocked by overexpression of the wild type Pitx2c N-terminal domain (upper panel on right) but not by variants in which the predicted interaction domain has been disrupted as in Pitx2c^lamatN-ter or the Pitx2c^L41AN-ter (L41A) mutants (lower panel on right).