The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice.
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 rostral head development in mice.
Song
J
J
Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Oh
S P
SP
Schrewe
H
H
Nomura
M
M
Lei
H
H
Okano
M
M
Gridley
T
T
Li
E
E
D030301:Activin Receptors, Type II; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D005775:Gastrula / Q000166:cytology; D006257:Head / Q000196:embryology; D017403:In Situ Hybridization; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D017978:Receptors, Growth Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology
D017931:DNA Primers; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D030301:Activin Receptors, Type II