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Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development |
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| Authors: | Dai Suzuki Atsushi Yamada Takanori Amano Rika Yasuhara Ayako Kimura Mizuho Sakahara Noriyuki Tsumaki Shu Takeda Masaru Tamura Masanori Nakamura Naoyuki Wada Tsutomu Nohno Toshihiko Shiroishi Atsu Aiba Ryutaro Kamijo |
| Affiliation: | a Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan b Mammalian Genetics Laboratory, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka, 411-0801, Japan c Department of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo 113-8519, Japan d Division of Molecular Genetics, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo, Kobe 650-0017, Japan e Department of Bone and Cartilage Biology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan f Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan g Department of Molecular and Developmental Biology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan |
| Abstract: | Developing vertebrate limbs are often utilized as a model for studying pattern formation and morphogenetic cell death. Herein, we report that conditional deletion of Rac1, a member of the Rho family of proteins, in mouse limb bud mesenchyme led to skeletal deformities in the autopod and soft tissue syndactyly, with the latter caused by a complete absence of interdigital programmed cell death. Furthermore, the lack of interdigital programmed cell death and associated syndactyly was related to down-regulated gene expression of Bmp2, Bmp7, Msx1, and Msx2, which are known to promote apoptosis in the interdigital mesenchyme. Our findings from Rac1 conditional mutants indicate crucial roles for Rac1 in limb bud morphogenesis, especially interdigital programmed cell death. |
| Keywords: | Bone morphogenetic proteins Conditional knockout mice Limb development Programmed cell death Rac1 Syndactyly |
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