Non-canonical Wnt pathway expression in the developing mouse and human retina

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• The non-canonical Wnt pathway is vital for tissue patterning and development.
• In mammals, it influences neuronal migration, dendritogenesis, axon growth, and synapse formation.
• Its specific role in human retinal development and synaptogenesis is not well understood.

Purpose of the Study:

• To investigate the role of the non-canonical Wnt pathway in human retinal development and synaptogenesis.
• To identify novel and species-specific genes involved in this process.
• To compare gene expression in mouse and human retinas, and human retinal organoids.

Main Methods:

• Analysis of single-cell RNA sequencing (scRNAseq) datasets from mouse and human retinas, and human retinal organoids.
• Examination of multiple developmental time points during outer retinal maturation.
• Validation of gene expression using fluorescence in situ hybridization (FISH).

Main Results:

• Identified ligands, receptors, and mediator genes with roles in retinal development, including novel and species-specific expressions.
• Demonstrated differential expression of non-canonical Wnt signaling components in developing mouse and human retinas during outer plexiform layer (OPL) development.
• Found distinct expression patterns for mouse and human FZD3 and WNT10A, and novel expression of mouse Wnt2b in starburst amacrine cells. Human retinal organoids mirrored human expression patterns.

Conclusions:

• Provides a foundational understanding of non-canonical Wnt signaling in mouse and human retinal development.
• Highlights species-specific differences in key Wnt pathway components.
• Suggests human retinal organoids are a viable model for studying non-canonical Wnt pathway expression.