Sox18 genetically interacts with VegfC to regulate lymphangiogenesis in zebrafish

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• Lymphangiogenesis, the formation of lymphatic vessels, is controlled by transcription factors and growth factor pathways.
• The interplay between these regulatory mechanisms is not fully understood.
• SOX18 and VEGFR3 mutations are linked to lymphedema, highlighting their importance.

Purpose of the Study:

• To investigate the interaction between transcription factor SOX18 and growth factor VEGFC in zebrafish lymphangiogenesis.
• To elucidate the role of SOX18 in early lymphatic development.
• To understand the crosstalk between SOX18 and VEGFC pathways.

Main Methods:

• Genetic interaction studies in zebrafish using morpholino knockdown of sox18 and vegfc.
• Utilized a novel transgenic line for inducible expression of a dominant-negative Sox18 mutant.
• Assessed lymphatic sprouting and thoracic duct formation.

Main Results:

• Sox18 knockdown selectively impaired lymphatic sprouting and thoracic duct formation.
• Sox18 and Sox7 exhibit redundant roles in arteriovenous differentiation.
• A synergistic interaction was observed between sox18 and vegfc knockdown, significantly affecting lymphatic development.

Conclusions:

• Sox18 plays a critical role in lymphangiogenesis post-arteriovenous differentiation.
• A previously unrecognized crosstalk exists between growth factor and transcription factor pathways in lymphangiogenesis.
• This interaction has implications for understanding lymphatic development and related diseases.