What mechanisms are responsible for asymmetric body patterning? To reach the top of the signalling cascade, Michael Levin and colleagues (p. ) have explored the role of the ion transporter H+-V-ATPase (V-ATPase) in regulating left-right (LR) asymmetry. Using a loss-of-function drug screen,they show that a V-ATPase inhibitor induces heterotaxia (the abnormal arrangement of organs) in Xenopus, zebrafish and chick. How does V-ATPase affect asymmetry? V-ATPase has two basic functions: to regulate pH and to regulate the membrane potential. By independently manipulating these pharmacologically and in other ways, the authors demonstrate that both are involved in establishing LR asymmetry in Xenopus. V-ATP subunits are expressed very early in Xenopus development, upstream of other early LR determinants. The authors propose that during early cleavage stages, the asymmetric localisation of V-ATPase creates a membrane potential gradient and a pH gradient, which combine to activate a small charged morphogen,precipitating an asymmetrical genetic cascade. They discuss ways of testing this model in other species.
