Publication: Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.
Loading...
Identifiers
Publication date
2021-01
Authors
Cahill, Thomas J
Sun, Xin
Ravaud, Christophe
Klaourakis, Konstantinos
Lupu, Irina-Elena
Lord, Allegra M
Browne, Cathy
Jacobsen, Sten Eirik W
Greaves, David R
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
The Company of Biologists
Metrics
Export
Abstract
Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distribution and prevalence of resident macrophages in the subepicardial compartment of the developing heart coincides with the emergence of new lymphatics, and that macrophages interact closely with the nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive vessel disruption, with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and foetal liver. Moreover, the Cx3cr1 + myeloid lineage was found to play essential functions in the remodelling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.
Description
Keywords
MeSH Terms
Lymphatic Vessels Animals CX3C Chemokine Receptor 1 Cell Adhesion Cell Line Endothelial Cells Gene Expression Regulation, Developmental Gene Knock-In Techniques Heart Humans Inflammation Lymphangiogenesis Macrophages Mice Mice, Inbred C57BL Organogenesis Receptors, Granulocyte-Macrophage Colony-Stimulating Factor Yolk Sac
DeCS Terms
Bibliographic citation
Development. 2021; 148(3):dev.194563