PUBLICATION

The brain vascular damage-induced lymphatic ingrowth is directed by Cxcl12b/Cxcr4a

Authors
Chen, J., He, J., Luo, L.
ID
ZDB-PUB-220614-11
Date
2022
Source
Development (Cambridge, England)   149(13): (Journal)
Registered Authors
He, Jianbo, Luo, Lingfei
Keywords
Cerebrovascular regeneration, Chemokine, Growth direction, Ingrown lymphatic vessels, Zebrafish
MeSH Terms
  • Animals
  • Brain/metabolism
  • Gene Expression Regulation, Developmental
  • Lymphatic Vessels*/metabolism
  • Receptors, CXCR4/genetics
  • Receptors, CXCR4/metabolism
  • Zebrafish*/genetics
PubMed
35694896 Full text @ Development
Abstract
After ischemic stroke, promotion of vascular regeneration without causing uncontrolled vessel growth appears to be the major challenge for pro-angiogenic therapies. The molecular mechanisms underlying how nascent blood vessels (BVs) are correctly guided into the post-ischemic infarction area remain unknown. Here, using zebrafish cerebrovascular injury model, we show that chemokine signaling provides critical guidance cues to determine the growing direction of ingrown lymphatic vessels (iLVs), and in turn that of nascent BVs. The chemokine receptor Cxcr4a is transcriptionally activated in the iLVs after injury, while its ligand Cxcl12b is expressed in the residual central BVs, the destinations of iLV ingrowth. Mutant and mosaic studies indicate that the Cxcl12b/Cxcr4a-mediated chemotaxis is necessary and sufficient to determine the growing direction of iLVs and nascent BVs. This study provides molecular basis how the vessel directionality of cerebrovascular regeneration is properly determined, suggesting potential application of Cxcl12b/Cxcr4a in the development of post-ischemic pro-angiogenic therapies.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes