RESTRICTED EXPRESSION OF TYPE-II TGF-BETA RECEPTOR IN MURINE EMBRYONIC-DEVELOPMENT SUGGESTS A CENTRAL ROLE IN TISSUE MODELING AND CNS PATTERNING

The type-II TGF beta receptor mediates many of the biological responses to TGF beta. An examination of the expression of the type-II TGF beta receptor during mouse embryogenesis therefore provides specific information about the role of TGF beta during embryogenesis than has been available to date. We have isolated the genomic murine homologue of the human type-II TGF beta receptor corresponding to exon 2. The murine and human sequences show a high degree of homology. Using the murine probe, we found that type-II TGF beta receptor expression is regulated in both a spatial and a temporal fashion by using in situ hybridization and ribonuclease protection assays. Type-II TGF beta receptor expression is localized to the mesenchyme during critical interactions with adjacent epithelium such as developing hair follicles, whisker follicles and tooth anlage. In the central nervous system, type-II TGF beta receptor expression is highly restricted to the floor plate. Strong expression is also detected in migrating neural crest cells, meninges, and choroid plexus. Specific mesenchymal localization of type-II TGF beta receptor is also observed in lung, kidney, intestine, stomach, and bladder. The restricted expression of type-II TGF beta receptor in mesenchymal cells at sites of epithelial-mesenchymal interactions suggests that type-II TGF beta receptor plays a major role in mediating the establishment of embryonic organ systems. The highly restricted expression of type-II TGF beta receptor in the developing CNS suggests an important role for a serine/threonine kinase in patterning of the nervous system.