Role of Six3 and Pax6 in regulating the gene networks involved in vertebrate eye development

Xenopus eye field transcription factors display a dynamic and overlapping expression pattern but their signaling hierarchy is unclear. Current signaling models are inconsistent with regard to some eye phenotypes. The object of my study is to clarify the role of some of the early and major players in eye development: is Rx1 really an upstream regulator of Pax6 and Six3 ? Its mutant phenotype is very much milder that those of the latter two. Morpholino-mediated Six3 knockdown caused severe phenotypes and absence of Pax6 expression in the eye field. Conversely, Pax6 knockdown produced a milder phenotype with reduced Six3 expression. Six3 phenotypes can be rescued by Pax6 , and perturbation of either demolishes Rx1 expression. This suggests a reversed order of dominance in signaling than previously described. I also examine the hierarchical relationships shared between Six3, Pax6, Rx1 and other eye field candidates - Otx2, Sox2, Pitx3, MafA, Lens1, Pax2 and gamma-crystallin