Identification of Pitx2c interaction partners

Evolutionarily conserved, asymmetric organ development and positioning is essential for normal embryonic development. Although many of the molecules that are important for asymmetric morphogenesis have been identified, the mechanisms that convert the ‘left’ and ‘right’ information into asymmetric organ morphogenesis and positioning remain elusive. The homeodomain transcription factor Pitx2c is asymmetrically expressed in the left lateral plate mesoderm and on the left sides of organs that become asymmetrically positioned within the embryo. Gain‐of‐function and loss‐of‐function experiments showed that Pitx2c participates in the development of left‐right asymmetries. We have demonstrated that overexpression of the wild‐type Pitx2c N‐terminus in ovo randomizes the direction of heart looping, the first morphological asymmetry conserved in vertebrate embryos. Leucine‐41 is critical for this effect. We hypothesize that the ectopically expressed Pitx2c N‐terminal domain competes with endogenous Pitx2c for binding to a partner required for asymmetric morphogenesis. We have screened embryonic and adult mouse yeast expression libraries to identify these partners. We have identified candidate interaction partners that unique to the embryonic library and those that were present in both libraries. This work has been funded by a CIHR Operating Grant to AKR.