A role for BMP signalling in heart looping morphogenesis in Xenopus.
Breckenridge, R.A., Mohun, T.J. and Amaya, E.
Development Biology 232:191-203 (2001) Full Article (500K)
Abstract
The heart develops from a linear tubular precursor, which loops to the right and undergoes terminal
differentiation to form the multi-chambered heart. Heart looping is the earliest manifestation of left-right
asymmetry, and determines the eventual heart situs. The signalling processes that impart laterality to the
unlooped heart tube, and thus allow the developing organ to interpret the left-right axis of the embryo are
poorly understood. Recent experiments in zebrafish led to the suggestion that bone morphogenetic protein
4 (BMP4) may impart laterality to the developing heart tube. Here we show that in Xenopus, as in
zebrafish, BMP4 is expressed predominantly on the left of the linear heart tube. Furthermore we
demonstrate that ectopic expression of Xenopus nodal-related protein 1 (Xnr1) RNA affect BMP4
expression in the heart, linking asymmetric BMP4 expression to the left-right axis. We show that
transgenic embryos overexpressing BMP4 bilaterally in the heart tube tend towards a randomization of
heart situs in an otherwise intact left-right axis. Additionally, inhibition of BMP signalling by expressing
noggin or a truncated, dominant negative BMP receptor prevents heart looping but allows the initial events
of chamber specification and anteroposterior morphogenesis to occur. Thus in Xenopus asymmetric
BMP4 expression links heart development to the left-right axis, by being both controlled by Xnr1
expression and being necessary for heart looping morphogenesis.
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