First published online April 12, 2006
Development 133, 901e (2006)
© The Company of Biologists Limited
Left-right from the top
What mechanisms are responsible for asymmetric body patterning? To reach
the top of the signalling cascade, Michael Levin and colleagues (p.
1657) 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.
Related articles in Development:
- Early, H+-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates
- Dany S. Adams, Kenneth R. Robinson, Takahiro Fukumoto, Shipeng Yuan, R. Craig Albertson, Pamela Yelick, Lindsay Kuo, Megan McSweeney, and Michael Levin
Development 2006 133: 1657-1671.
[Abstract]
[Full Text]
