The transcription factor Maz is essential for normal eye development

Area of Science:

• Developmental Biology
• Genetics
• Ophthalmology

Background:

• Wnt/β-catenin signaling is vital for proper eye development.
• Dysregulation of this pathway leads to ocular malformations due to impaired cell fate and differentiation.
• The Myc-associated zinc-finger (Maz) gene's role in eye development is largely unexplored.

Purpose of the Study:

• To investigate the role of Maz in ocular development.
• To determine the impact of Maz disruption on Wnt/β-catenin signaling in the eye.
• To identify MAZ gene variants associated with human ocular development abnormalities.

Main Methods:

• Targeted gene inactivation of Maz in mice.
• Analysis of Wnt cascade gene expression (Sfrp2, Wnt2b, Fzd4) and Wnt reporter activity (TCF-Lef1).
• Molecular analysis of Maz's role in Wnt pathway activation and ciliary margin patterning.
• Identification of copy-number and single-nucleotide variants of MAZ in humans with ocular defects.

Main Results:

• Maz disruption in mice led to increased expression of Wnt cascade genes (Sfrp2, Wnt2b, Fzd4) but paradoxically decreased Wnt reporter activity.
• Maz deficiency caused abnormal peripheral eye formation and reduced progenitor cell proliferation.
• Maz is essential for Wnt/β-catenin pathway activation and ciliary margin patterning.
• MAZ variants were identified in humans with abnormal ocular development, linking it to chromosome 16p11.2 copy-number variants.

Conclusions:

• Maz is a critical transcriptional regulator of ocular development.
• Maz disruption impairs Wnt/β-catenin signaling, leading to developmental eye defects.
• MAZ variants contribute to eye comorbidities associated with chromosome 16p11.2 copy-number variants.