AP-2 alpha transcription factor is required for early morphogenesis of thelens vesicle

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-2 alpha in early morphogenesis of the eye by examining the nature of the ocular defects in AP-2 alpha null and c himeric mice. AP-2 alpha null embryos exhibited ocular phenotypes ranging f rom a complete lack of eyes (anophthalmia) to defects in the developing len s involving a persistent adhesion of the lens to the overlying surface ecto derm. Two genes involved in lens development and differentiation, Pax6 and MIP26 were also misexpressed. AP-2 alpha mutants also exhibited defects in the optic cup consisting of transdifferentiation of the dorsal retinal pigm ented epithelium into neural retina and the absence of a defined ganglion c ell layer. Newly generated chimeric embryos consisting of a population of A P-2 alpha(-/-) and AP-2 alpha(+/+) cells exhibit ocular defects similar to those seen in the knockout embryos. Immunolocalization of AP-2 proteins (al pha, beta, and gamma) to the normal developing eye revealed both unique and overlapping expression patterns, with AP-2 alpha expressed in a number of the ocular tissues that exhibited defects in the mutants, including the dev eloping lens where AP-2 alpha is uniquely expressed. Together these finding s demonstrate a requirement for AP-2 alpha in early morphogenesis of the ey e. (C) 1999 Academic Press.