Signaling by the transforming growth factor-beta (TGF-beta) ligands occur through different mechanisms of which the receptor-II/receptor-I mediated pathway is the prominently studied pathway. Signals are conveyed through serine-threonine kinase receptors at the cell surface to specific intracellular mediators, the Smad proteins. Activation of Smad proteins results in their translocation to the nucleus and subsequent activation of gene expression. The pathway mentioned here shows mechanisms delineated as deduced from knockout models and stem cell data. The role of ELF (a beta spectrin) in TGF beta signaling is shown during early stages development.