Tissue-localized macrophages is the origin of pericytes in mouse embryonic skin vasculature

Authors

• T Yamazaki
• A Nalbandian
• S Abdelazim
• Y Uchida
• W Li
• TD Arnold
• Y Kubota
• M Ema
• Y Mukouyama

Abstract

Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) are essential for vascular network formation and maintenance. Despite the significance of pericytes in preserving vascular integrity, the origin of pericytes in the developing vasculature has been elusive. Here we show the first evidence that pericytes are derived from tissue-localized macrophages in the developing skin vasculature. Whole-mount immunohistochemical analysis revealed that NG2+ and platelet derived growth factor receptor (PDGFR) ß+ pericytes are detectable in the primary capillary plexus at embryonic day 12.5 (E12.5). Pericyte coverage preceded vascular smooth muscle cells on smaller branches, and its distribution began in the arterial vasculature. To determine their developmental origin in the skin, we conducted a series of in vivo fate-mapping experiments using different cell type-specific Cre lines, revealing that tissue macrophages appear to generate pericytes in the skin. Furthermore FACS-isolated tissue-macrophages from embryonic skins give rise to NG2+ and PDGFRß+ pericytes in vitro. To further investigate whether tissue-macrophages are required for the pericyte development in vivo, we examined pericyte development in PU.1 mutants lacking tissue-macrophages in the skin. Although their vascular network appears to be normal, the mutants failed to develop pericytes in the skin. Defective pericyte coverage was also present in Csf1op/op mutants with decreased number of macrophages, albeit a milder phenotype. Taken together, our data indicates that pericytes in the developing skin vasculature originate from tissue-macrophages.

Scientific Focus Area: Developmental Biology

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