Functional analysis of activins during mammalian development.
Activins are dimeric (beta A beta A; beta B beta B; beta A beta B) members of the transforming growth factor-beta superfamily. They are widely expressed during murine development, are highly conserved during vertebrate evolution, and may be involved in mesoderm induction and neurulation in Xenopus laevis and Oryzias latipes. To investigate the function of mammalian activins in vivo, we generated mice with mutations either in activin-beta A or in both activin-beta A and activin-beta B. Activin-beta A-deficient mice develop to term but die within 24 h of birth. They lack whiskers and lower incisors and have defects in their secondary palates, including cleft palate, demonstrating that activin-beta A must have a role during craniofacial development. Mice lacking both activin subunits show the defects of both individual mutants but no additional defects, indicating that there is no functional redundancy between these proteins during embryogenesis. In contrast to observations in lower vertebrates, zygotic expression of activins is not essential for mesoderm formation in mice.
Matzuk
M M
MM
Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
Kumar
T R
TR
Vassalli
A
A
Bickenbach
J R
JR
Roop
D R
DR
Jaenisch
R
R
Bradley
A
A
D028341:Activins; D000818:Animals; D002460:Cell Line; D005314:Embryonic and Fetal Development / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology*; D007265:Inhibins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010159:Palate / Q000002:abnormalities / Q000196:embryology; D012886:Skull / Q000002:abnormalities / Q000196:embryology; D016212:Transforming Growth Factor beta / Q000502:physiology
D006133:Growth Substances; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins