TY - JOUR
T1 - The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice
AU - Song, Jihwan
AU - Oh, Suk P.
AU - Schrewe, Heinrich
AU - Nomura, Masatoshi
AU - Lei, Hong
AU - Okano, Makiko
AU - Gridley, Thomas
AU - Li, En
N1 - Funding Information:
We thank Dr. E. Robertson for generously providing nodal mutant mice and Drs. R. Beddington, B. Herrmann, B. Hogan, A. Joyner, A. McMahon, and J. Rossant for in situ probes. This work was supported by grants from Bristol–Myers Squibb and NIH GM52106 (E.L), a fellowship from the Wellcome Trust (J.S.), a National Research Service Award (NIH) (S.P.O), and a fellowship from the Japanese Society for the Promotion of Science (M.N.).
PY - 1999/9/1
Y1 - 1999/9/1
N2 - The type II activin receptors, ActRIIA and ActRIIB, have been shown to play critical roles in axial patterning and organ development in mice. To investigate whether their function is required for mesoderm formation and gastrulation as implicated in Xenopus studies, we generated mice carrying both receptor mutations by interbreeding the ActRIIA and ActRIIB knockout mutants. We found that embryos homozygous for both receptor mutations were growth arrested at the egg cylinder stage and did not form mesoderm. Further analyses revealed that ActRIIA(-/-) ActRIIB(+/-) and about 15% of the ActRIIA(-/-) embryos failed to form an elongated primitive streak, resulting in severe disruption of mesoderm formation in the embryo proper. Interestingly, we observed similar gastrulation defects in ActRIIA(-/- )nodal(+/-) double mutants, which, if they developed beyond the gastrulation stage, displayed rostral head defects and cyclopia. These results provide genetic evidence that type II activin receptors are required for egg cylinder growth, primitive streak formation, and rotral head development in mice.
AB - The type II activin receptors, ActRIIA and ActRIIB, have been shown to play critical roles in axial patterning and organ development in mice. To investigate whether their function is required for mesoderm formation and gastrulation as implicated in Xenopus studies, we generated mice carrying both receptor mutations by interbreeding the ActRIIA and ActRIIB knockout mutants. We found that embryos homozygous for both receptor mutations were growth arrested at the egg cylinder stage and did not form mesoderm. Further analyses revealed that ActRIIA(-/-) ActRIIB(+/-) and about 15% of the ActRIIA(-/-) embryos failed to form an elongated primitive streak, resulting in severe disruption of mesoderm formation in the embryo proper. Interestingly, we observed similar gastrulation defects in ActRIIA(-/- )nodal(+/-) double mutants, which, if they developed beyond the gastrulation stage, displayed rostral head defects and cyclopia. These results provide genetic evidence that type II activin receptors are required for egg cylinder growth, primitive streak formation, and rotral head development in mice.
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U2 - 10.1006/dbio.1999.9370
DO - 10.1006/dbio.1999.9370
M3 - Article
C2 - 10452853
AN - SCOPUS:0033198507
SN - 0012-1606
VL - 213
SP - 157
EP - 169
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -