Critical roles for murine Reck in the regulation of vascular patterning and stabilization

• Published in: Scientific reports 2015-12, Vol.5 (1), p.17860-17860, Article 17860
• Main Authors: de Almeida, Glícia Maria, Yamamoto, Mako, Morioka, Yoko, Ogawa, Shuichiro, Matsuzaki, Tomoko, Noda, Makoto
• Format: Article
• Language: English
• Subjects: 13; 13/106; 13/51; 14; 631/136/16; 631/67/581; 64; 64/60; Alleles; Angiogenesis; Animals; Aorta; Blood Vessels - metabolism; Cell interactions; Embryogenesis; Embryonic growth stage; Explants; Extracellular matrix; Extracellular Matrix - metabolism; Female; Fibronectin; Fibronectins - metabolism; Gene Silencing; Gestation; GPI-Linked Proteins - deficiency; GPI-Linked Proteins - genetics; GPI-Linked Proteins - metabolism; Humanities and Social Sciences; Lethality; Matrix metalloproteinase; Metalloproteinase; Mice; Mice, Knockout; Mice, Transgenic; Microvessels - metabolism; Molecular modelling; multidisciplinary; Mutation; Neovascularization, Physiologic - genetics; Organ Specificity - genetics; Rodents; Science; Tumor suppressor genes
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep17860

Extracellular matrix (ECM) is known to play several important roles in vascular development, although the molecular mechanisms behind these remain largely unknown. RECK , a tumor suppressor downregulated in a wide variety of cancers, encodes a membrane-anchored matrix-metalloproteinase-regulator. Mice lacking functional Reck die in utero , demonstrating its importance for mammalian embryogenesis; however, the underlying causes of mid-gestation lethality remain unclear. Using Reck conditional knockout mice, we have now demonstrated that the lack of Reck in vascular mural cells is largely responsible for mid-gestation lethality. Experiments using cultured aortic explants further revealed that Reck is essential for at least two events in sprouting angiogenesis; (1) correct association of mural and endothelial tip cells to the microvessels and (2) maintenance of fibronectin matrix surrounding the vessels. These findings demonstrate the importance of appropriate cell-cell interactions and ECM maintenance for angiogenesis and the involvement of Reck as a critical regulator of these events.