Bm. Johansson et Mv. Wiles, EVIDENCE FOR INVOLVEMENT OF ACTIVIN-A AND BONE MORPHOGENETIC PROTEIN-4 IN MAMMALIAN MESODERM AND HEMATOPOIETIC DEVELOPMENT, Molecular and cellular biology, 15(1), 1995, pp. 141-151
Xenopus in vitro studies have implicated both transforming growth fact
or beta (TGF-beta) and fibroblast growth factor (FGF) families in meso
derm induction. Although members of both families are present during m
ouse mesoderm formation, there is little evidence for their functional
role in mesoderm induction. We show that mouse embryonic stem cells,
which resemble primitive ectoderm, can differentiate to mesoderm in vi
tro in a chemically defined medium (CDM) in the absence of fetal bovin
e serum. In CDM, this differentiation is responsive to TGF-beta family
members in a concentration dependent manner, with activin A mediating
the formation of dorsoanterior-like mesoderm and bone morphogenetic p
rotein 4 mediating the formation of ventral mesoderm, including hemato
poietic precursors. These effects are not observed in CDM alone or whe
n TGF-beta 1, -beta 2, or -beta 3, acid FGF, or basic FGF is added ind
ividually to CDM. In vivo, at day 6.5 of mouse development, activin be
ta A RNA is detectable in the decidua and bone morphogenetic protein 4
RNA is detectable in the egg cylinder. Together, our data strongly im
plicate the TGF-beta family in mammalian mesoderm development and hema
topoietic cell formation.