BMP type II receptor is required for gastrulation and early development of mouse embryos.
Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta superfamily, play a variety of roles during mouse development. BMP type II receptor (BMPR-II) is a type II serine/threonine kinase receptor, which transduces signals for BMPs through heteromeric complexes with type I receptors, including activin receptor-like kinase 2 (ALK2), ALK3/BMPR-IA, and ALK6/BMPR-IB. To elucidate the function of BMPR-II in mammalian development, we generated BMPR-II mutant mice by gene targeting. Homozygous mutant embryos were arrested at the egg cylinder stage and could not be recovered at 9.5 days postcoitum. Histological analysis revealed that homozygous mutant embryos failed to form organized structure and lacked mesoderm. The BMPR-II mutant embryos are morphologically very similar to the ALK3/BMPR-IA mutant embryos, suggesting that BMPR-II is important for transducing BMP signals during early mouse development. Moreover, the epiblast of the BMPR-II mutant embryo exhibited an undifferentiated character, although the expression of tissue-specific genes for the visceral endoderm was essentially normal. Our results suggest that the function of BMPR-II is essential for epiblast differentiation and mesoderm induction during early mouse development.
Beppu
H
H
Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Research for the Future Program, Japan Society for the Promotion of Science, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo, 170-8455, Japan.
Kawabata
M
M
Hamamoto
T
T
Chytil
A
A
Minowa
O
O
Noda
T
T
Miyazono
K
K
D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II; D002454:Cell Differentiation; D002678:Chimera / Q000235:genetics; D005314:Embryonic and Fetal Development; D005775:Gastrula / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting / Q000379:methods; D005838:Genotype; D006651:Histocytochemistry; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; C498219:Bmpr2 protein, mouse; D052006:Bone Morphogenetic Protein Receptors, Type II