Expression of activin subunits, activin receptors and follistatin in postimplantation mouse embryos suggests specific developmental functions for different activins

Abstract

Using in situ hybridization we have studied the localization of the messenger RNAs encoding the inhibin/activin subunits (alpha, beta A, beta B), the activin-binding protein follistatin and activin receptors (IIA, IIB) in mouse embryos during postimplantation development. From 6.5- to 9.5-days post coitum (p.c.) activin beta A and beta B subunit expression was restricted to the decidua, while activin receptor type IIB messages were exclusively detected in the embryo. Expression of activin receptor type IIA was apparent in the embryo as early as 9.5 days p.c. In contrast, follistatin transcripts were present in both the decidua and the embryo at the early postimplantation stages. In particular, the primitive streak region, specific rhombomeres in the developing hindbrain, somites, paraxial mesoderm and parietal endoderm cells attached to the Reichert's membrane showed strong expression of follistatin. In 10.5- and 12.5-day embryos expression of the beta A subunit message was abundant in mesenchymal tissue, in particular in the developing face, the body wall, the heart, precartilage condensations in the limb and in the mesenchyme of structures that show both epithelial and mesenchymal components, including tissues of the embryonic digestive, respiratory and genital tracts. The distribution of beta B transcripts was quite different from that observed for beta A. beta B is strongly expressed in selected regions of the brain, in particular the fore- and hindbrain, and in the spinal cord. Specific hybridization signals were also present in the epithelium of the stomach and oesophagus. Common sites of beta A and beta B expression are blood vessels, intervertebral disc anlagen, mesenchymal condensations in the flank region and the gonad primordium. The latter organ is the only site in the embryo where the alpha subunit is expressed, and thus where inhibit activity may be present. During the period of organogenesis the sites of expression of activin receptors type IIA and IIB messenger RNA (mRNA) generally coincide with or are adjacent to the sites of beta subunit expression. Differences in the expression patterns of the receptor RNAs are the whisker follicles, where type IIA is expressed, and the metanephros and the forebrain where type IIB transcripts are present. Taken together, the present data suggest that follistatin, but not one of the known activin forms (A,B,AB) is involved in early postimplantation development.(ABSTRACT TRUNCATED AT 400 WORDS)