The transformation suppressor gene Reck is required for postaxial patterning in mouse forelimbs
Mako Yamamoto,
Tomoko Matsuzaki,
Rei Takahashi,
Eijiro Adachi,
Yasuhiro Maeda,
Sachiyo Yamaguchi,
Hitoshi Kitayama,
Michiko Echizenya,
Yoko Morioka,
David B. Alexander,
Takeshi Yagi,
Shigeyoshi Itohara,
Takashi Nakamura,
Haruhiko Akiyama,
Makoto Noda
Affiliations
Mako Yamamoto
Department of Molecular Oncology
Tomoko Matsuzaki
Department of Molecular Oncology
Rei Takahashi
Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395, Japan
Eijiro Adachi
Department of Matrix Biology and Regenerative Medicine, Kitasato University Graduate School of Medical Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan
Yasuhiro Maeda
Department of Molecular Oncology
Sachiyo Yamaguchi
Department of Molecular Oncology
Hitoshi Kitayama
Department of Molecular Oncology
Michiko Echizenya
Department of Molecular Oncology
Yoko Morioka
Department of Molecular Oncology
David B. Alexander
Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan
Takeshi Yagi
KOKORO-biology group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan
Shigeyoshi Itohara
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Takashi Nakamura
Department of Orthopaedic and Musculoskeletal Surgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan
Haruhiko Akiyama
Department of Orthopaedic and Musculoskeletal Surgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan
Summary The membrane-anchored metalloproteinase-regulator RECK has been characterized as a tumor suppressor. Here we report that mice with reduced Reck-expression show limb abnormalities including right-dominant, forelimb-specific defects in postaxial skeletal elements. The forelimb buds of low-Reck mutants have an altered dorsal ectoderm with reduced Wnt7a and Igf2 expression, and hypotrophy in two signaling centers (i.e., ZPA and AER) that are essential for limb outgrowth and patterning. Reck is abundantly expressed in the anterior mesenchyme in normal limb buds; mesenchyme-specific Reck inactivation recapitulates the low-Reck phenotype; and some teratogens downregulate Reck in mesenchymal cells. Our findings illustrate a role for Reck in the mesenchymal-epithelial interactions essential for mammalian development.
