Hedgehog signalling: How cholesterol modulates the signal

Developing embryos are replete with a variety of potent signalling proteins, the activities of which must be precisely regulated for development to follow its proper course. In principle, such signals may take two distinct forms. Proteins tethered to the membrane of a signalling cell — for instance via a transmembrane domain or lipid modification — might be expected to act as short-range switches, influencing the behaviour of their nearest neighbours in an essentially binary fashion. By contrast, proteins that are secreted by expressing cells could act over relatively long distances, with the potential to influence cell fate in a dose-dependent manner. In practice, however, some signalling proteins have been found to possess characteristics of both of these idealised forms.