Involvement of the Reck tumor suppressor protein in maternal and embryonic vascular remodeling in mice
1 Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan
2 Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, 2-2-3 Minatojima Minami, Chuou-ku, Kobe 650-0047, Japan
3 Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 420-707, Korea
4 Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe 610-0395, Japan
5 Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabedohri, Mizuho-ku, Nagoya 467-8603, Japan
6 Cancer Research Institute, Kanazawa University, Kakuma-cho, Kanazawa, Ishikawa 920-1192, Japan
7 Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
BMC Developmental Biology 2010, 10:84 doi:10.1186/1471-213X-10-84Published: 6 August 2010
Developmental angiogenesis proceeds through multiple morphogenetic events including sprouting, intussusception, and pruning. Mice lacking the membrane-anchored metalloproteinase regulator Reck die in utero around embryonic day 10.5 with halted vascular development; however, the mechanisms by which this phenotype arises remain unclear.
We found that Reck is abundantly expressed in the cells associated with blood vessels undergoing angiogenesis or remodelling in the uteri of pregnant female mice. Some of the Reck-positive vessels show morphological features consistent with non-sprouting angiogenesis. Treatment with a vector expressing a small hairpin RNA against Reck severely disrupts the formation of blood vessels with a compact, round lumen. Similar defects were found in the vasculature of Reck-deficient or Reck conditional knockout embryos.
Our findings implicate Reck in vascular remodeling, possibly through non-sprouting angiogenesis, in both maternal and embyornic tissues.