Open Access Highly Accessed Research article

Involvement of the Reck tumor suppressor protein in maternal and embryonic vascular remodeling in mice

Ediriweera PS Chandana1, Yasuhiro Maeda1, Akihiko Ueda1, Hiroshi Kiyonari2, Naoko Oshima2, Mako Yamamoto1, Shunya Kondo1, Junseo Oh3, Rei Takahashi4, Yoko Yoshida1, Satoshi Kawashima1, David B Alexander5, Hitoshi Kitayama1, Chiaki Takahashi6, Yasuhiko Tabata7, Tomoko Matsuzaki1 and Makoto Noda1*

Author Affiliations

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

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BMC Developmental Biology 2010, 10:84  doi:10.1186/1471-213X-10-84

Published: 6 August 2010

Abstract

Background

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.

Results

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.

Conclusions

Our findings implicate Reck in vascular remodeling, possibly through non-sprouting angiogenesis, in both maternal and embyornic tissues.