Smads and early developmental signaling by the TGFβ superfamily

Members of the transforming growth factor β (TGFβ) superfamily of peptide growth factors regulate a broad range of cellular functions, including proliferation, apoptosis, extracellular matrix secretion and adhesion, terminal differentiation, and specification of developmental fate (Roberts and Sporn 1993; Wall and Hogan 1994; Moses and Serra 1996). Although regulation of each of these functions by TGFβ superfamily factors is important throughout embryonic development, it is the potency of these factors in regulating developmental fate that has been the focus of recent excitement among embryologists. This has been primarily because of indications in both vertebrate and invertebrate model systems that TGFβs can serve as morphogens, acting across developing tissues in a graded fashion to specify a patterned array of cell fates (Gurdon et al. 1994; Nellen et al. 1996; Neumann and Cohen 1997). A defining feature of morphogens is their ability to specify multiple cell types over a range of concentrations. This capacity has been demonstrated for several members of the TGFβ superfamily in early Xenopus embryos (Green and Smith 1990; Dosch et al. 1997; Wilson et al. 1997) and for the bone morphogenetic protein (BMP) homolog decapentaplegic(dpp) in the early Drosophila embryo and wing disc (Gelbart 1989; Ferguson and Anderson 1992; Wharton et al. 1993; Lecuit et al. 1996; Nellen et al. 1996). The intracellular mechanisms by which ligand dose can be transduced into multiple developmental fates is therefore a current focus of interest for understanding TGFβs as morphogens.

A second striking feature of TGFβ superfamily signals is the variety of effects they can evoke, contingent on the developmental history of the responding cell. For example, at the gastrula stage, BMP2 can specify frog blastomeres as epidermal rather than neural progenitors (Wilson et al. 1997); at later stages it …