The functional recovery of tissue after an ischemic stroke requires the formation of new blood vessels (BVs) by neoangiogenesis. Although many factors are known to regulate neoangiogenesis, the molecular mechanisms that promote directional neoangiogenesis – without causing uncontrolled vessel growth – are less well characterized. Now, Lingfei Luo and colleagues reveal that damage-induced lymphatic growth and, in turn, vascular growth in the zebrafish brain is directed by Cxcr4a/Cxcl12b signalling. Using a cerebrovascular injury model, the authors show that the chemokine receptor Cxcr4a is transcriptionally activated in ingrowing lymphatic vessels (iLVs) in response to injury. Its ligand, Cxcl12b, is expressed in residual central BVs, towards which the iLVs grow. By examining cxcr4a and cxcl12b mutants, the researchers demonstrate that Cxcr4a/Cxcl12b are required for determining the directionality of iLV growth; in these mutants, iLVs lose their directionality and exhibit increased branching, and this is accompanied by uncontrolled BV formation and branching. Finally, the authors report that ectopically expressed Cxcl12b can attract iLVs towards sites of ectopic expression. In summary, these findings highlight a role for Cxcr4a/Cxcl12b signalling in controlling vessel patterning during cerebrovascular regeneration.
