Craniofacial malformation in R-spondin2 knockout mice.
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.
Yamada
Wakako
W
Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
Nagao
Kenji
K
Horikoshi
Kaori
K
Fujikura
Ayako
A
Ikeda
Eiji
E
Inagaki
Yoshimasa
Y
Kakitani
Makoto
M
Tomizuka
Kazuma
K
Miyazaki
Hiroshi
H
Suda
Toshio
T
Takubo
Keiyo
K
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
D019699:Thrombospondins; D051153:Wnt Proteins; D051176:beta Catenin; C518904:RSPO2 protein, mouse; D000098907:R-Spondins