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Developmental biology

Controlling the cellular brakes

Nature volume 401, pages 657–658 (1999)Cite this article

How does a cell decide to become a nerve cell and not, say, an endothelial cell? Its fate lies with certain ‘master’ genes, which switch on cellular programmes to differentiate precursor cells into, for example, nerve, muscle or heart tissue. Differentiation is thought to be kept in check by molecular brakes, and, on page 670 of this issue, Lyden et al.1 discuss the importance of these brakes for correct development of both the neuronal system (neurogenesis) and new blood vessels (angiogenesis). The authors also report that endothelial cells switch on these differentiation brakes during tumour angiogenesis. So, by manipulating them, perhaps angiogenesis — and, hence, tumour formation — can be blocked.

Considering the complexity of cell-fate determination, it is no surprise that bHLH proteins need to be counter-regulated. In 1990, Benezraet al.4 identified the ‘inhibitor of differentiation’ (Id) proteins as potential cellular brakes to prevent premature cell differentiation. Subsequent studies revealed that Id proteins can affect cell fate in a diverse manner. Although they lack the basic DNA-binding domain, Id proteins can form ‘non-functional’ heterodimers with bHLH factors — that is, they act as dominant-negative regulators of bHLH proteins3 (Fig. 1b). Class A bHLH proteins tend to associate strongly with Id proteins, whereas the class B proteins bind poorly. However, Id proteins may affect class B bHLH proteins by sequestering their class A partners.

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Figure 1: Relationships between the basic helix–loop–helix (bHLH) and ‘inhibitor of differentiation’ (Id) proteins, and cell-fate determination.

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  1. the Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Campus Gasthuisberg, Herestraat 49, University of Leuven, Leuven, B-3000, Belgium

    Peter Carmeliet

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Correspondence to Peter Carmeliet.

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Carmeliet, P. Controlling the cellular brakes. Nature 401, 657–658 (1999). https://doi.org/10.1038/44304

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