The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye

Area of Science:

• Developmental Biology
• Molecular Biology
• Teratology

Background:

• Maternal diabetes is a known risk factor for congenital abnormalities, including embryopathies.
• Hyperglycemia associated with diabetes can disrupt critical developmental pathways.
• The non-canonical Wnt-Planar Cell Polarity (PCP) pathway plays a role in embryonic development.

Purpose of the Study:

• To investigate the role of the Wnt-PCP pathway in mouse eye development.
• To determine how maternal diabetes and hyperglycemia affect the Wnt-PCP pathway during embryogenesis.
• To elucidate the link between Wnt-PCP pathway disruption and ocular defects in diabetic embryopathy.

Main Methods:

• Analysis of Wnt-PCP pathway gene expression (e.g., Daam1, Vangl2) in embryos from diabetic and control dams.
• Utilizing mouse models with specific genotypes for Daam1 (Daam1(gt/gt), Daam1(gt/+)).
• In vitro exposure of embryonic cells to glucose to assess pathway gene expression and cellular changes.

Main Results:

• Maternal diabetes downregulates Wnt-PCP pathway components like Daam1 and Vangl2.
• Daam1 deficiency (Daam1(gt/gt) and Daam1(gt/+)) leads to ocular defects (anophthalmia/microphthalmia).
• Embryos from diabetic dams with the Daam1(gt/+) genotype exhibit more severe embryopathy.
• In vitro glucose exposure alters Wnt-PCP gene expression, cytoskeletal organization, cell shape, and polarity in the optic vesicle.

Conclusions:

• The Wnt-PCP pathway is essential for early mouse eye development.
• Diabetes-induced hyperglycemia disrupts the Wnt-PCP pathway, leading to altered cell morphology and polarity.
• Disruption of the Wnt-PCP pathway by diabetes is a key mechanism underlying the ocular phenotype in affected embryos.