Purpose - The scaffold protein Axin2 is an antagonist and universal target of the Wnt/β-catenin pathway. Disruption of Axin2 may lead to developmental eye defects; however, this has not been examined. The purpose of this study was to investigate the role of Axin2 during ocular and extraocular development in mouse.
Methods - Animals heterozygous and homozygous for a Axin2lacZ knock-in allele were analyzed at different developmental stages for reporter expression, morphology as well as for the presence of ocular and extraocular markers using histologic and immunohistochemical techniques.
Results - During early eye development, the Axin2lacZ reporter was expressed in the periocular mesenchyme, RPE, and optic stalk. In the developing retina, Axin2lacZ reporter expression was initiated in ganglion cells at late embryonic stages and robustly expressed in subpopulations of amacrine and horizontal cells postnatally. Activation of the Axin2lacZ reporter overlapped with labeling of POU4F1, PAX6, and Calbindin. Germline deletion of Axin2 led to variable ocular phenotypes ranging from normal to severely defective eyes exhibiting microphthalmia, coloboma, lens defects, and expanded ciliary margin. These defects were correlated with abnormal tissue patterning in individual affected tissues, such as the optic fissure margins in the ventral optic cup and in the expanded ciliary margin.
Conclusions - Our results reveal a critical role for Axin2 during ocular development, likely by restricting the activity of the Wnt/β-catenin pathway.