TGF-β Family Signaling in Mesenchymal Differentiation

SIGNALING BY TRANSFORMING GROWTH FACTOR-β (TGF-β) family factors affects many distinct differentiation pathways, including those of the hematopoietic and immune cell lineages, epithelial lineages, and heman-gioblasts. Similarly, TGF-β family signaling has revealed that it is a major regulatory network that drives lineage selection and differentiation progres-sion in mesenchymal cells. As with other systems, the signaling activity of TGF-β family members correlates with the temporal and spatial regulation of TGF-β family ligand, receptor, and Smad expression, each of which is regulated during mesenchymal cell differentiation. Likewise, the activities of the ligands, receptors, and Smads are also regulated during differentia-tion. For example, ligand activity is dictated by secreted antagonists or lig-and-binding proteins. Receptors are activated through autocrine and paracrine signaling. Smad activity is defined by combinatorial interactions and cross-talk with other signaling pathways, and the Smads then serve t