Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development.
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.
Suzuki
Dai
D
Department of Biochemistry, Showa University, Hatanodai, Shinagawa, Tokyo, Japan.
Yamada
Atsushi
A
Amano
Takanori
T
Yasuhara
Rika
R
Kimura
Ayako
A
Sakahara
Mizuho
M
Tsumaki
Noriyuki
N
Takeda
Shu
S
Tamura
Masaru
M
Nakamura
Masanori
M
Wada
Naoyuki
N
Nohno
Tsutomu
T
Shiroishi
Toshihiko
T
Aiba
Atsu
A
Kamijo
Ryutaro
R
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D017931:DNA Primers; D005819:Genetic Markers; D007150:Immunohistochemistry; D018878:Limb Buds / Q000196:embryology*; D008648:Mesoderm / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D051153:Wnt Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
D017931:DNA Primers; D005819:Genetic Markers; D051153:Wnt Proteins; D020830:rac1 GTP-Binding Protein