AP-2α transcription factor is required for early morphogenesis of the lens vesicle

Abstract

AP-2 transcription factors are a family of retinoic acid-responsive genes, which are involved in complex morphogenetic processes. In the current study, we determine the requirement for AP-2α in early morphogenesis of the eye by examining the nature of the ocular defects in AP-2α null and chimeric mice. AP-2α null embryos exhibited ocular phenotypes ranging from a complete lack of eyes (anophthalmia) to defects in the developing lens involving a persistent adhesion of the lens to the overlying surface ectoderm. Two genes involved in lens development and differentiation, Pax6 and MIP26 were also misexpressed. AP-2α mutants also exhibited defects in the optic cup consisting of transdifferentiation of the dorsal retinal pigmented epithelium into neural retina and the absence of a defined ganglion cell layer. Newly generated chimeric embryos consisting of a population of AP-α(-/-) and AP- 2α(+/+) cells exhibit ocular defects similar to those seen in the knockout embryos. Immunolocalization of AP-2 proteins (α, β, and γ) to the normal developing eye revealed both unique and overlapping expression patterns, with AP-2α expressed in a number of the ocular tissues that exhibited defects in the mutants, including the developing lens where AP-2α is uniquely expressed. Together these findings demonstrate a requirement for AP-2α in early morphogenesis of the eye.