Transforming growth factor-beta signalling in extraembryonic mesoderm is required for yolk sac vasculogenesis in mice

We have analysed the function of transforming growth factor beta (TGF-beta) in yolk sac development in mice by generating somatic chimaeras in which t he extraembryonic mesoderm, which gives rise to the endothelial and haemato poietic cells of the yolk sac vasculature, is derived from embryonic stem ( ES) cells. The ES cells were stably transfected and express either the full -length type II binding receptor or a kinase-deficient mutant of this recep tor. Examination of yolk sacs from chimaeras between E8.5 and 9.5, and anal ysis of marker expression in embryoid bodies from these mutant ES cell line s in prolonged suspension culture demonstrated that (1) a major function of TGF-beta in yolk sac mesoderm is to regulate production and deposition of fibronectin in the extracellular matrix that maintains yolk sac integrity, (2) TGF-beta signalling is not required for differentiation of extraembryon ic mesoderm into endothelial cells but is necessary for their subsequent or ganisation into robust vessels, and (3) TGF-beta signalling must be tightly regulated for the differentiation of primitive haematopoietic cells to tak e place normally. Together, these results show that defective TGF-beta sign alling in the extraembryonic mesoderm alone is sufficient to account for th e extraembryonic phenotype reported previously in TGF-beta 1(-/-) mice (Dic kson, M. C., Martin, J. S., Cousins, F. M., Kulkarni, A. B., Karlsson, S, a nd Akhurst, R. J. (1995) Development 121, 1845-1854).