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First published online 11 October 2006
doi: 10.1242/dev.02647

Development 133, 4463-4473 (2006)
Published by The Company of Biologists 2006
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Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis

Makoto Ikeya1, Masako Kawada1, Hiroshi Kiyonari2, Noriaki Sasai1, Kazuki Nakao2, Yasuhide Furuta3 and Yoshiki Sasai1,*

1 Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
2 Laboratory for Animal Resources and Genetic Engineering, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
3 Department of Biochemistry and Molecular Biology, M. D. Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.

* Author for correspondence (e-mail: sasaicdb{at}mub.biglobe.ne.jp)

Accepted 8 September 2006

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.

Key words: Crossveinless 2 (Bmper), Mouse, Organogenesis, Gene targeting, Crim2




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