Alterations in the spatiotemporal expression of the chemokine receptor CXCR4 in endothelial cells cause failure of hierarchical vascular branching

Wenling Li, Chengyu Liu, Nathan Burns, Jeffery Hayashi, Atsufumi Yoshida, Aparna Sajja, Sara González-Hernández, Ji Liang Gao, Philip M. Murphy, Yoshiaki Kubota, Yong Rui Zou, Takashi Nagasawa, Yoh suke Mukouyama

Research output: Contribution to journalArticlepeer-review

Abstract

The C-X-C chemokine receptor CXCR4 and its ligand CXCL12 play an important role in organ-specific vascular branching morphogenesis. CXCR4 is preferentially expressed by arterial endothelial cells, and local secretion of CXCL12 determines the organotypic pattern of CXCR4+ arterial branching. Previous loss-of-function studies clearly demonstrated that CXCL12-CXCR4 signaling is necessary for proper arterial branching in the developing organs such as the skin and heart. To further understand the role of CXCL12-CXCR4 signaling in organ-specific vascular development, we generated a mouse model carrying the Cre recombinase-inducible Cxcr4 transgene. Endothelial cell-specific Cxcr4 gain-of-function embryos exhibited defective vascular remodeling and formation of a hierarchical vascular branching network in the developing skin and heart. Ectopic expression of CXCR4 in venous endothelial cells, but not in lymphatic endothelial cells, caused blood-filled, enlarged lymphatic vascular phenotypes, accompanied by edema. These data suggest that CXCR4 expression is tightly regulated in endothelial cells for appropriate vascular development in an organ-specific manner.

Original languageEnglish
Pages (from-to)70-84
Number of pages15
JournalDevelopmental Biology
Volume477
DOIs
Publication statusPublished - 2021 Sep

Keywords

  • CXCL12
  • CXCR4
  • Coronary development
  • Gain-of-function
  • Lymphatic vessel development
  • Vascular development

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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