The role of Pax6 transcription factor in development of the anterior segment

Abstract

AbstractEye development is extremely sensitive to the levels of Pax6. Reduction in the levels of Pax6 in heterozygotes for a Pax6 null allele results in ocular abnormalities including Aniridia in humans and Small eye in mice and rat. In the complete absence of Pax6 protein in Pax6‐deficient mice lens induction does not occur, and the neural retina as well as retinal pigment epithelium do not differentiate. It is well established that Pax6 function is required both in the lens placode and in the optic vesicle. Conditional gene inactivation in mice concomitant with lens induction established the critical and cell‐autonomous role of Pax6 for subsequent lens formation. Similarly, optic vesicle deficient for Pax6 transcription factor fails to develop into a proper neural retina. We used CRISPR/Cas9 genome engineering to mutagenize Pax6 gene in a mouse model. We were able to generate novel alleles of Pax6 that manifest profound lens phenotypes without showing apparent phenotypic changes in the neural retina or retinal pigment epithelium. Our data indicate an extreme sensitivity of early stages of lens development for the presence of intact, fully functional Pax6 protein.