The role of transcription factors involved in TGF beta superfamily signaling during development

Recent studies of transforming growth factor-beta (TGF-beta) signaling have identified a signaling pathway that includes Ser/Thr kinase transmembrane receptors, intracellular substrates and transducers of receptor activation known as Smads, and DNA-binding transcription factors that are regulated by interaction with Smads. Both genetic and biochemical studies show that Sma ds are central mediators of TGF-beta signaling. How do Smads regulate the e xpression of target genes in the nucleus? Over the past three years, transc ription factors involved in TGF-beta signaling have been identified and the molecular events in the nucleus have begun to be understood. Both Smads, w hich have intrinsic DNA binding activity, and additional transcription fact ors, act together to regulate the expression of target genes in the nucleus . Smads are relatively ubiquitously expressed in embryos during the develop ment, while interacting transcription factors are expressed with a restrict ed pattern, either temporally or spatially. Therefore the developmental spe cificity of TGF-beta signaling may be, at least in part, determined by cell -type specific transcription factors.