title: Critical roles for murine Reck in the regulation of vascular patterning and stabilization.
abstract: 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.
authors.affiliation: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho; Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Glícia Maria
authors.initials: GM
authors.lastname: de Almeida
authors.affiliation: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Mako
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Morioka
authors.affiliation: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Noda
mesh_terms: D000483:Alleles; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D020868:Gene Silencing; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055806:Microvessels / Q000378:metabolism; D009154:Mutation; D018919:Neovascularization, Physiologic / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics
chemical_list: D005353:Fibronectins; D058851:GPI-Linked Proteins; C492025:Reck protein, mouse