Reviews & Analysis

During development, stem and progenitor cells gradually commit to differentiation pathways. Cell fate decisions are regulated by differentiation factors, which activate transcription programmes that specify lineage and differentiation status. Among these factors, the transforming growth factor (TGF)-β family is important in both lineage selection and progression of differentiation of most, if not all, cell and tissue types. There is now increasing evidence that TGF-β family proteins have the ability to redirect the differentiation of cells that either have fully differentiated or have engaged in differentiation along a particular lineage, and can thereby elicit 'transdifferentiation'. This capacity for cellular plasticity is critical for normal embryonic development, but when recapitulated in the adult it can give rise to, or contribute to, a variety of diseases. This is illustrated by the ability of TGF-β family members to redirect epithelial cells into mesenchymal differentiation and to cause switching of mesenchymal cells from one lineage to another. Hence, various pathologies in adults may be considered diseases of abnormal development and differentiation.

During development, embryonic cells sculpt three-dimensional tissues. Although cell polarity is commonly analysed along one, and sometimes two, dimensions, this perspective illustrates how higher-order cell polarity regulates convergent extension — the coordinated cell rearrangement that produces solid tissue elongation.

The Hedgehog (Hh) pathway plays central roles in animal development and stem-cell function. Defects in Hh signalling lead to birth defects and cancer in humans. The first and often genetically damaged step in this pathway is the interaction between two membrane proteins — Patched (Ptc), encoded by a tumour suppressor gene, and Smoothened (Smo), encoded by a proto-oncogene. Recent work linking Hh signalling to sterol metabolites and protein-trafficking events at the primary cilium promises to shed light on the biochemical basis of how Patched inhibits Smoothened, and to provide new avenues for cancer treatment.