IGF-II promotes mesoderm formation

IGF-II is abundant in the nascent mesoderm of the gastrulating mouse embryo . Its function at this developmental stage is unknown. We investigated it b y following the in vitro and in vivo differentiation of several androgeneti c, biparental, parthenogenetic, and androgenetic Igf2 -/- murine ES cell li nes; these cells differed in endogenous IGF-II levels because Igf2 is pater nally expressed in the mouse embryo in most tissues. The expression of meso derm markers and the subsequent formation of muscle structures were correla ted with endogenous IGF-II level during teratoma formation and during in vi tro differentiation. In addition, the absence of Igf2 in androgenetic Igf2 -/- ES cells led to a severe impairment of mesoderm development, demonstrat ing the dependence of the preferential mesoderm development of androgenetic ES cells upon Igf2 activity, among the numerous known imprinted genes. The addition of exogenous IGF-II to in vitro differentiation culture medium le d to a specific increase in the expression of mesoderm markers. Thus, we pr opose a novel model in which the binding of IGF-II to its principal signali ng receptor, IGF1R, at the surface of mesoderm precursor cells increases th e formation of mesoderm cells. (C) 2000 Academic Press.