The transcription factor Maz is essential for normal eye development.

Wnt/β-catenin signaling plays an essential role in eye development. Faulty regulation of this pathway results in ocular malformations due to defects in cell fate determination and differentiation. Herein we show that disruption of Maz, the gene encoding Myc-associated zinc finger transcription factor, produces developmental eye defects in mice and humans. Expression of key genes involved in the Wnt cascade, Sfrp2, Wnt2b and Fzd4 were significantly increased in mice with targeted inactivation of Maz, resulting in abnormal peripheral eye formation with reduced proliferation of the progenitor cells in the region. Paradoxically, the Wnt reporter TCF-Lef1 displayed a significant downregulation in Maz-deficient eyes. Molecular analysis indicates that Maz is necessary for the activation of the Wnt/β-catenin pathway and participates in the network controlling ciliary margin patterning. Copy number variations and single nucleotide variants of MAZ were identified in humans that result in abnormal ocular development. The data support MAZ as a key contributor to the eye comorbidities associated with chromosome 16p11.2 copy number variants and as a transcriptional regulator of ocular development.