Cell interactions modulate embryonal carcinoma cell differentiation into parietal or visceral endoderm

Abstract

F9 is a clonal line of mouse teratocarcinoma-derived embryonal carcinoma (EC) cells which shows very little spontaneous differentiation in vivo or in vitro¹. Recently, however, it was reported^2–6 that F9 monolayers treated with retinoic acid and dibutyryl cyclic AMP differentiate into an early embryonic cell type known as parietal endoderm, which is one of two distinct populations of extra-embryonic endoderm that differentiate in the normal mouse embryo shortly after implantation^7,8. The other population is the visceral endoderm, and the two differ not only in their morphology and location within the embryo, but also in their biochemical properties^9–12. Parietal endoderm cells, for example, do not synthesize α-fetoprotein¹³ (AFP), whereas visceral endoderm cells do¹³. There is evidence⁸ that during embryogenesis parietal and visceral endoderm are derived from a common precursor population known as the primary endoderm, and recent experiments with cultured mouse embryos¹⁴ suggest that the phenotype of these cells can be modulated by contact with different embryonic tissues. We now show that if F9 EC cultures are treated with retinoic acid when they are in the form of small aggregates, they differentiate on the outer surface cells which morphologically resemble visceral rather than parietal endoderm. In addition, the cells synthesize and secrete AFP, identified by immunoprecipitation and immunoperoxidase reactions using specific anti-AFP immunoglobulin. One interpretation of this result is that F9 cells treated with retinoic acid differentiate first into multipotent cells analogous to the primary endoderm of the normal embryo which then express either the mature parietal or visceral phenotype depending on the nature of the intercellular contact signals they receive. We therefore believe that F9 EC cells may be even more useful than previously supposed for biochemical studies on factors controlling gene expression during mammalian embryogenesis.