Deep Insight Section

Transforming growth factor β (TGFβ) is the prototype member of a large superfamily of cytokines that also includes the bone morphogenic proteins (BMPs), growth and differentiation factors (GDFs) and activins. There are three genes for TGFβ in humans and mice (TGFβ1, TGFβ2 and TGFβ3) that each encode ~25 kDa mature, processed proteins and share over 70% identity in their amino acid sequences. Despite this identity in protein structure, homozygous deletion of individual TGFβ genes reveals distinct functions for each isoform (Dünker and Krieglstein, 2000). TGFβ1 knockout mice appear normal at birth but quickly succumb to a diffuse and lethal inflammation at approximately 3 weeks. Deletion of TGFβ2 or TGFβ3 is perinatal lethal, with TGFβ2 mice demonstrating a wide range of developmental defects and TGFβ3 mice displaying abnormal pulmonary development. Both TGFβ2 and TGFβ3 knockout mice exhibit cleft palates. These observations highlight the broad involvement of TGFβ cytokines in mammalian physiology, as would be anticipated given the wide distribution of TGFβ expression and cell-responsiveness among tissues. More important to this review, however, is the idea that the clear role for TGFβ in development points to a prominent role for these cytokines in cell proliferation and apoptosis.