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A role for BMP signalling in heart looping morphogenesis in Xenopus
R A Breckenridge1, T J Mohun, E Amaya
1Wellcome/CRC Institute, Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom.
Developmental Biology
|March 20, 2001
Summary
Bone morphogenetic protein 4 (BMP4) is crucial for heart development, linking left-right asymmetry to heart looping. Asymmetric BMP4 expression, controlled by Xnr1, is essential for proper heart situs determination in Xenopus embryos.
Area of Science:
- Developmental Biology
- Cardiovascular Research
- Molecular Signaling
Background:
- Heart development involves looping, establishing left-right asymmetry and determining heart situs.
- The molecular mechanisms underlying heart tube laterality and left-right axis interpretation are not fully understood.
- Previous studies in zebrafish suggested a role for bone morphogenetic protein 4 (BMP4) in heart tube laterality.
Purpose of the Study:
- To investigate the role of BMP4 in heart development and laterality in Xenopus.
- To elucidate the relationship between BMP4, Xnr1, and heart looping.
- To understand how asymmetric BMP4 expression links heart development to the embryonic left-right axis.
Main Methods:
- Expression analysis of BMP4 in Xenopus linear heart tubes.
- Ectopic expression of Xenopus nodal-related protein 1 (Xnr1) RNA.
- Overexpression of BMP4 bilaterally in the heart tube.
- Inhibition of BMP signaling using noggin or a dominant-negative BMP receptor.
Main Results:
- BMP4 is predominantly expressed on the left side of the linear heart tube in Xenopus, similar to zebrafish.
- Ectopic Xnr1 expression influences BMP4 expression, linking it to the left-right axis.
- Bilateral BMP4 overexpression randomizes heart situs.
- BMP signaling inhibition prevents heart looping but permits chamber specification and anteroposterior morphogenesis.
Conclusions:
- Asymmetric BMP4 expression in Xenopus is essential for heart looping morphogenesis.
- BMP4 acts as a key molecular link between the left-right axis and heart development.
- BMP4's role in heart laterality is conserved across species, highlighting its fundamental importance.