Role of pitx genes in embryonic pattern formation

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We have been studying a regulatory gene, Pitx3, that has been linked to eye malformations and cataracts in humans. Pitx3 presumably normally acts to coordinate the activities of other genes necessary to the formation of a lens and retina. When mutated, the gene has similar effects in mice, however all of the mutant mice and human patients characterized to date likely retain partial gene function. Pitx3 plays a similar role in frogs, an organism that is routinely employed to study eye development and genetics. However we have noticed other anomalies in mutant frogs that suggest additional roles for Pitx3 in establishing a body plan for embryos: Pitx3 plays a role in correctly orienting asymmetrical organs such as stomach, intestine, heart, gall bladder etc. In addition, the gene appears to play a role in regulating the segmentation of precursors to the vertebrae. We have employed a technique called microarray analysis to identify likely downstream targets (other genes) of Pitx3 activity. We have isolated some of these genes, and we are currently trying to understand how Pitx3 coordinates their participation in the regulatory networks that construct eye, vertebrae, and asymmetrical visceral organs. Characterizing the gene networks involved in segmentation and left/right asymmetry is important for helping us to understand how spinal, heart, and eye defects arise in humans.