Patterning of angiogenesis in the zebrafish embryo

Area of Science:

• Developmental Biology
• Vascular Biology
• Genetics

Background:

• Embryonic vascular pattern generation is poorly understood.
• Zebrafish trunk vasculature exhibits a highly regular pattern of intersegmental vessels (ISVs) connecting the aorta to the dorsal longitudinal anastomotic vessel (DLAV).
• Understanding the cellular and genetic mechanisms governing ISV formation is critical for developmental biology.

Purpose of the Study:

• To define the cellular origins, migratory paths, and cell fates contributing to trunk ISV formation in zebrafish.
• To identify genetic factors that regulate the precise patterning of angiogenic growth.
• To elucidate the role of somite-derived signals in guiding ISV development.

Main Methods:

• Lineage analysis using laser activation of caged dye and mosaic construction to trace angioblast origins and migration.
• ENU mutagenesis screen to identify mutations affecting ISV patterning.
• Analysis of mutant embryos and morphants (VEGF) to assess gene function and signaling pathways.

Main Results:

• Angioblasts for ISVs originate in the lateral posterior mesoderm, migrate to the dorsal aorta, and then sprout between somites.
• ISVs exhibit distinct cell fates and migratory paths, with ventral sprouting and dorsal extension guided by different cues.
• The 'out of bounds' (obd) mutation causes precocious and anomalous ISV sprouting, indicating somite-derived inhibitory signals regulate sprouting position.

Conclusions:

• Zebrafish ISVs provide a tractable model for studying vessel development and pattern formation.
• The 'out of bounds' gene and inhibitory signals from ventral somites are critical for constraining angiogenic sprouting to the correct intersomitic position.
• This study defines key cellular and genetic elements governing the precise patterning of embryonic vasculature.