Expression of TGF-beta s and their receptors during implantation and organogenesis of the mouse embryo.

The spatial and temporal expression of the transforming growth factor beta (TGF-beta) receptors type III, type II, and two types I (ALK-5 and Tsk 7L) and their ligands TGF-beta 1 and TGF-beta 2 in postimplantation mouse development were examined using the reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. With RT-PCR, expression of the signaling TGF-beta receptors (types II and ALK-5) was shown to be absent in isolated germ layers of 6.0-7.5 days postcoitum (dpc) embryos, whereas the type III receptor and Tsk 7L were differentially expressed at these stages. In contrast, all TGF-beta receptor types were expressed at these stages in the pregnant uterus and decidua. TGF-beta 1 and TGF-beta 2 transcripts were detected before gastrulation at 6.5 dpc only in the visceral embryonic endoderm, whereas during gastrulation, at 7.5 dpc TGF-beta 1 and TGF-beta 2 mRNA was detected in all three germ layers. In situ hybridization and immunohistochemistry of the expression of the TGF-beta type II receptor confirmed the data obtained by RT-PCR. Furthermore, the type II receptor was detected in the extraembryonic ectoderm of 7.5 dpc embryos. In the embryo proper, TGF-beta type II receptor expression was detected only later in differentiating tissues and developing organs, but not in the brain and neural tube. Since the expression of the type II receptor may essentially determine whether a cell is able to respond to TGF-beta, the results are consistent with the view that TGF-beta s might be implicated in embryo implantation and organogenesis, but are not involved in gastrulation of the embryo.