title: Craniofacial malformation in R-spondin2 knockout mice.
abstract: In vertebrates, craniofacial formation is accomplished by synergistic interaction of many small elements which are generated independently from distinct germ layers. Because of its complexity, the imbalance of one signaling cascade such as Wnt/beta-catenin pathway easily leads to craniofacial malformation, which is the most frequent birth defect in humans. To investigate the developmental role of a newly identified activator of Wnt/beta-catenin signaling, Rspo2, we generated and characterized Rspo2(-/-) mice. We found CLP with mild facial skeletal defects in Rspo2(-/-) mice. Additionally, Rspo2(-/-) mice also exhibited distal limb loss and lung hypoplasia, and died immediately after birth with respiratory failure. We showed the apparent reduction of Wnt/beta-catenin signaling activity at the branchial arch and the apical ectodermal ridge in Rspo2(-/-) mice. These findings indicate that Rspo2 regulates midfacial, limb, and lung morphogenesis during development through the Wnt/beta-catenin signaling.
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Yamada
authors.forename: Kenji
authors.initials: K
authors.lastname: Nagao
authors.forename: Kaori
authors.initials: K
authors.lastname: Horikoshi
authors.forename: Ayako
authors.initials: A
authors.lastname: Fujikura
authors.forename: Eiji
authors.initials: E
authors.lastname: Ikeda
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Inagaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kakitani
authors.forename: Kazuma
authors.initials: K
authors.lastname: Tomizuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.forename: Keiyo
authors.initials: K
authors.lastname: Takubo
mesh_terms: D000818:Animals; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000378:metabolism; D005121:Extremities / Q000196:embryology; D017880:Limb Deformities, Congenital / Q000235:genetics; D008168:Lung / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D019699:Thrombospondins / Q000235:genetics*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000098907:R-Spondins
chemical_list: D019699:Thrombospondins; D051153:Wnt Proteins; D051176:beta Catenin; C518904:RSPO2 protein, mouse; D000098907:R-Spondins