Monocyte-Derived cxcl12 Guides a Directional Migration of Blood Vessels in Zebrafish

Sprouting blood vessels, reaching the aimed location, and establishing the proper connections are vital for building vascular networks. Such biological processes are subject to precise molecular regulation. So far, the mechanistic insights into understanding how blood vessels grow to the correct position are limited. In particular, the guide cues and the signaling-originating cells remain elusive.

Live imaging analysis was used to observe the vascular developmental process of zebrafish. Whole-mount in situ hybridization and fluorescent in situ hybridization were used to detect the expression profiles of the genes. Single-cell sequencing analysis was conducted to identify the guiding protein and its originating cells.

Taking advantage of live imaging analysis, we described a directional blood vessel migration in the vascularization process of zebrafish pectoral fins. We demonstrated that pectoral fin vessel c migrated over long distances and was anastomosed with the second pair of intersegmental vessels. Furthermore, we found the cxcl12a-cxcr4a axis specifically guided this long-distance extension of pectoral fin vessel c-intersegmental vessel, and either inhibition or overexpression of cxcl12a-cxcr4a signaling both mislead the growth of pectoral fin vessel c to ectopic areas. Finally, based on an analysis of single-cell sequencing data, we revealed that a population of monocytes expresses the Cxcl12a, which guides the migration of the vascular sprout.

Our study identified Cxcl12a as the signaling molecule for orchestrating the organotypic-specific long-distance migration and anastomosis of the pectoral fin vessel and the intersegmental vessels in zebrafish. We discovered a specific cluster of gata1 (globin transcription factor 1)-positive monocytes responsible for expressing Cxcl12a. The findings offer novel insights into the mechanisms underlying organotypic vascularization in vertebrates.