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
  • Lymphatic Vessels*/metabolism
  • Receptors, CXCR4/genetics
  • Receptors, CXCR4/metabolism
  • Gene Expression Regulation, Developmental
  • Brain/metabolism
  • Zebrafish*/genetics
  • Animals
(all 7)
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
No images available
Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cq10TgTransgenic Insertion
    cq14TgTransgenic Insertion
      cq15TgTransgenic Insertion
        cq25TgTransgenic Insertion
          cq26TgTransgenic Insertion
            cq27TgTransgenic Insertion
              mu100
                Indel
                ncv34TgTransgenic Insertion
                  nim5TgTransgenic Insertion
                    um20
                      Small Deletion
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      No data available
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CreEFGCre
                      Dendra2EFGDendra2
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GAL4FFEFGGAL4FF
                      KALTA4EFGKALTA4
                      mCherryEFGmCherry
                      NTREFGNTR
                      TagRFPEFGTagRFP
                      VenusEFGVenus
                      1 - 10 of 10
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                      Mapping