title: Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development.
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.
authors.affiliation: Department of Biochemistry, Showa University, Hatanodai, Shinagawa, Tokyo, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Suzuki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamada
authors.forename: Takanori
authors.initials: T
authors.lastname: Amano
authors.forename: Rika
authors.initials: R
authors.lastname: Yasuhara
authors.forename: Ayako
authors.initials: A
authors.lastname: Kimura
authors.forename: Mizuho
authors.initials: M
authors.lastname: Sakahara
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tsumaki
authors.forename: Shu
authors.initials: S
authors.lastname: Takeda
authors.forename: Masaru
authors.initials: M
authors.lastname: Tamura
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamura
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Wada
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nohno
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiroishi
authors.forename: Atsu
authors.initials: A
authors.lastname: Aiba
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kamijo
mesh_terms: 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*
chemical_list: D017931:DNA Primers; D005819:Genetic Markers; D051153:Wnt Proteins; D020830:rac1 GTP-Binding Protein