Transforming growth factor-β (TGF-β) is a group of multi- functional regulatory polypeptides that are secreted by a large variety of cells and play a crucial role in cell proliferation, differentiation, migration and extracellular matrix production

Transforming growth factor-β (TGF-β) is a group of multifunctional regulatory polypeptides that are secreted by a large variety of cells and play a crucial role in cell proliferation, differentiation, migration and extracellular matrix production (reviewed by Roberts and Sporn, 1990; Massagué, 1990; Moses et al., 1990, Derynck, 1994). Based on these activities and its expression during embryogenesis, it is widely assumed that TGF-β has important functions in mammalian development. Three closely related isoforms of TGF-β (TGF-β1, TGFβ2 and TGF-β3) have been characterized and are expressed at different sites in a defined temporal and spatial pattern during mouse development (Fitzpatrick et al., 1990; Pelton et al., 1990a,b, 1991). Thus it is expected that each of these isoforms has a distinct role in fetal development. The inactivation of the mouse TGF-β1 gene has been shown to result in a wasting syndrome with diffuse inflammatory infiltrates in homozygous animals (Shull et al., 1992; Kulkarni et al., 1993). It is likely that redundancy with TGF-β2 and TGF-β3 in many tissues prevented embryonic manifestation of the phenotype. Based on their patterns of expression during mouse embryogenesis (Fitzpatrick et al., 1990; Pelton et al., 1990a,b, 1991), inactivation of the TGF-β2 and TGF-β3 genes will likely result in phenotypes that are markedly different from the TGF-β1 gene inactivation. The structural differences among their precursor segments (Derynck et al., 1988; ten Dijke et al., 1988), which interact with the mature homodimeric TGF-β isoforms and confer latency (Miyazono et al., 1988, 1991), suggest that there may be distinct differences in the posttranslational activation of the latent complexes. However, the biological activities of the mature, activated factors are largely similar although there are some remarkable quantitative differences (Ohta et al., 1987; Jennings et al., 1988; Graycar et al., 1989, Lyons et al., 1991). How TGF-β exerts its multiplicity of biological effects is still largely unclear. Up to eight cell surface proteins with the capacity to interact with TGF-β have been detected (Massagué, 1992). Among these, three types of TGF-β receptors are commonly observed on most cells. The type III receptor, also known as betaglycan, is a cell surface proteoglycan and thought not to function as a signal transducing molecule (Lopez-Casillas et al., 1991; Wang et al., 1991). Genetic evidence has clearly implicated the type I and type II receptors as responsible for most if not all biological activities of TGF-β (Laiho et al., 1990, 1991; Geiser et al., 1992). Specific inactivation of the type II receptor indicates that, at least in the epithelial Mv1Lu cells, the type II receptor 165 Development 120, 165-175 (1994) Printed in Great Britain  The Company of Biologists Limited 1994