Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis.
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.
Ikeya
Makoto
M
Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
Kawada
Masako
M
Kiyonari
Hiroshi
H
Sasai
Noriaki
N
Nakao
Kazuki
K
Furuta
Yasuhide
Y
Sasai
Yoshiki
Y
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002356:Cartilage / Q000196:embryology*; D017931:DNA Primers; D005123:Eye / Q000196:embryology*; D007150:Immunohistochemistry; D007668:Kidney / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D038081:Organogenesis / Q000502:physiology*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
D002352:Carrier Proteins; D017931:DNA Primers; C517553:crossveinless 2 protein, mouse; C501622:kielin-chordin-like protein, mouse