Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye

The Pax6 transcription factor plays a key role in ocular development of ver tebrates and invertebrates. Homozygosity of the Pax6 null mutation in human and mice results in arrest of optic vesicle development and failure to ini tiate lens formation. This phenotype obscures the understanding of autonomo us function of Pax6 in these tissue components and during later development al stages. We employed the Cre/loxP approach to inactivate Pax6 specificall y in the eye surface ectoderm concomitantly with lens induction. Although l ens induction occurred in the mutant, as indicated by Sore up-regulation in the surface ectoderm, further development of the lens was arrested. Hence, Pax6 activity was found to be essential in the specified ectoderm for lens placode formation. Furthermore, this mutant model allowed us for the first time to address in vivo the development of a completely normal retina in t he absence of early lens structures. Remarkably, several independent, fully differentiated neuroretinas developed in a single optic vesicle in the abs ence of a lens, demonstrating that the developing lens is not necessary to instruct the differentiation of the neuroretina but is, rather, required fo r the correct placement of a single retina in the eye.