During vertebrate lens development, the lens placode undergoes a carefully programmed morphogenetic process that leads to the formation of a lens with relatively undifferentiated, proliferative epithelial cells in the anterior of the lens, and highly differentiated, mitotically inactive fiber cells in the posterior of the lens (for review, see McAvoy et al.,1999; Chow and Lang,2001; Donner et al.,2006; Cvekl and Duncan,2007; Medina-Martinez and Jamrich,2007). The proliferation and differentiation of the lens cells are controlled by several transcription factors. While the transcription factor Pax6 appears to be the key regulator of lens development, as mutations in this gene lead to eye malformations in humans (Ton et al.,1991; Jordan et al.,1992; Glaser et al.,1994; Hanson et al.,1994), mice, and rats (Hill et al.,1991; Fujiwara et al.,1994), several other transcriptional regulators are also critical for lens formation. One of them is the homeodomain-containing factor Pitx3. Pitx3 is expressed during early vertebrate lens development. A double deletion that eliminates the promoter region and a part of the coding region of this gene causes the abnormal lens phenotype in the mouse line aphakia (ak; Semina et al.,2000; Rieger et al.,2001) and mutations in PITX3 lead to the development of autosomal-dominant cataract in humans (Semina et al.,1998). In ak mice, the lens begins to form, but its development is abnormal. Eventually, lens development arrests and the lens disappears (Varnum and Stevens,1968; Zwaan,1975; Zwaan and Kirkland,1975; Grimm et al.,1998). Some aspects of lens development in the aphakia mutant are similar to the lens development in Foxe3 null mice (Medina-Martinez et al.,2005). In both mutants, the invaginating lens placode does not separate properly from the head surface ectoderm and the lens remains connected to the surface ectoderm with a stalk (Varnum and Stevens,1968; Zwaan,1975; Zwaan and Kirkland,1975; Grimm et al.,1998; Blixt et al.,2000,2007; Brownell et al.,2000; Medina-Martinez et al.,2005; Medina-Martinez and Jamrich,2007). Foxe3 is a conserved forkhead transcription factor that is critical for lens development in several vertebrate species (for review, see Medina-Martinez and Jamrich,2007). Mutations in this gene, or its altered expression, cause abnormal lens development in mouse, humans, and zebrafish (Blixt et al.,2000; Brownell et al.,2000; Semina et al.,2001; Ormestad et al.,2002; Medina-Martinez et al.,2005; Shi et al.,2006; Valleix et al.,2006; Medina-Martinez and Jamrich,2007; Swindell et al.,2008).