Ikeya Makoto, Kawada Masako, Kiyonari Hiroshi, Sasai Noriaki, Nakao Kazuki, Furuta Yasuhide, Sasai Yoshiki
Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
Development. 2006 Nov;133(22):4463-73. doi: 10.1242/dev.02647. Epub 2006 Oct 11.
We here report essential roles of the Bmp-binding protein crossveinless 2 (Cv2; Bmper) in mouse organogenesis. In the null Cv2 mutant mouse, gastrulation occurs normally, but a number of defects are found in Cv2-expressing tissues such as the skeleton. Cartilage differentiation by Bmp4 treatment is reduced in cultured Cv2(-/-) fibroblasts. Moreover, the defects in the vertebral column and eyes of the Cv2(-/-) mouse are substantially enhanced by deleting one copy of the Bmp4 gene, suggesting a pro-Bmp role of Cv2 in the development of these organs. In addition, the Cv2(-/-) mutant exhibits substantial defects in Bmp-dependent processes of internal organ formation, such as nephron generation in the kidney. This kidney hypoplasia is synergistically enhanced by the additional deletion of Kcp (Crim2) which encodes a pro-Bmp protein structurally related to Cv2. This study demonstrates essential pro-Bmp functions of Cv2 for locally restricted signal enhancement in multiple aspects of mammalian organogenesis.
我们在此报告Bmp结合蛋白交叉无脉2（Cv2；Bmper）在小鼠器官发生中的重要作用。在Cv2基因敲除突变小鼠中，原肠胚形成正常，但在表达Cv2的组织如骨骼中发现了许多缺陷。在培养的Cv2（-/-）成纤维细胞中，Bmp4处理诱导的软骨分化减少。此外，通过删除一个Bmp4基因拷贝，Cv2（-/-）小鼠的脊柱和眼睛缺陷显著增强，表明Cv2在这些器官发育中具有促进Bmp的作用。此外，Cv2（-/-）突变体在依赖Bmp的内脏器官形成过程中表现出严重缺陷，如肾脏中的肾单位生成。通过额外删除编码与Cv2结构相关的促Bmp蛋白的Kcp（Crim2），这种肾发育不全协同增强。本研究证明了Cv2在哺乳动物器官发生的多个方面对局部受限信号增强具有重要的促Bmp功能。
