An in vivo method to quantify lymphangiogenesis in zebrafish

Area of Science:

• Developmental biology
• Vascular biology
• Zebrafish models

Background:

• Lymphangiogenesis is crucial in disease pathogenesis.
• Existing in vivo models for lymphangiogenesis lack physiological relevance.
• Zebrafish offer a transparent and rapidly developing model for in vivo studies.

Purpose of the Study:

• To establish a method for quantifying lymphatic growth in vivo using zebrafish.
• To assess the impact of lymphangiogenesis modulators on lymphatic development in zebrafish.

Main Methods:

• Utilized late-phase microangiography to visualize trunk lymphatic capillaries in zebrafish (2-3 days post-fertilization).
• Measured real-time changes in lymphatic capillary development in response to various modulators.
• Introduced recombinant human vascular endothelial growth factor (VEGF)-C, transplanted human endothelial and mouse melanoma cells, and used morpholino-based knockdown of vegfc and chemical inhibitors.

Main Results:

• Recombinant human VEGF-C and cell transplantation increased lymphatic capillary growth.
• Knockdown of vegfc and chemical inhibitors decreased lymphatic capillary growth.
• Demonstrated that modulators of lymphangiogenesis affect lymphatic capillary development in zebrafish.

Conclusions:

• Late-phase microangiography enables quantification of lymphatic capillaries in embryonic and larval zebrafish.
• Human activators and inhibitors, along with transplanted cells, modulate zebrafish lymphatic capillary development.
• This model allows for rapid screening of lymphangiogenesis modulators and elucidation of lymphatic development pathways.