Yamada Wakako, Nagao Kenji, Horikoshi Kaori, Fujikura Ayako, Ikeda Eiji, Inagaki Yoshimasa, Kakitani Makoto, Tomizuka Kazuma, Miyazaki Hiroshi, Suda Toshio, Takubo Keiyo
Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
Biochem Biophys Res Commun. 2009 Apr 10;381(3):453-8. doi: 10.1016/j.bbrc.2009.02.066. Epub 2009 Feb 20.
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.
在脊椎动物中，颅面形成是由许多小元件协同相互作用完成的，这些小元件由不同的胚层独立产生。由于其复杂性，诸如Wnt/β-连环蛋白信号通路等一个信号级联的失衡很容易导致颅面畸形，这是人类最常见的出生缺陷。为了研究新鉴定的Wnt/β-连环蛋白信号激活剂Rspo2的发育作用，我们生成并鉴定了Rspo2(-/-)小鼠。我们在Rspo2(-/-)小鼠中发现了伴有轻度面部骨骼缺陷的腭裂。此外，Rspo2(-/-)小鼠还表现出远端肢体缺失和肺发育不全，并在出生后因呼吸衰竭立即死亡。我们发现Rspo2(-/-)小鼠鳃弓和顶端外胚层嵴处的Wnt/β-连环蛋白信号活性明显降低。这些发现表明，Rspo2在发育过程中通过Wnt/β-连环蛋白信号调节面中部、肢体和肺的形态发生。
