Elsevier

Developmental Biology

Volume 305, Issue 2, 15 May 2007, Pages 577-588
Developmental Biology

Zebrafish Bmp4 regulates left–right asymmetry at two distinct developmental time points

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Abstract

Left–right (LR) asymmetry is regulated by early asymmetric signals within the embryo. Even though the role of the bone morphogenetic protein (BMP) pathway in this process has been reported extensively in various model organisms, opposing models for the mechanism by which BMP signaling operates still prevail. Here we show that in zebrafish embryos there are two distinct phases during LR patterning in which BMP signaling is required. Using transgenic lines that ectopically express either noggin3 or bmp2b, we show a requirement for BMP signaling during early segmentation to repress southpaw expression in the right lateral plate mesoderm and regulate both visceral and heart laterality. A second phase was identified during late segmentation, when BMP signaling is required in the left lateral plate mesoderm to regulate left-sided gene expression and heart laterality. Using morpholino knock down experiments, we identified Bmp4 as the ligand responsible for both phases of BMP signaling. In addition, we detected bmp4 expression in Kupffer's vesicle and show that restricted knock down of bmp4 in this structure results in LR patterning defects. The identification of these two distinct and opposing activities of BMP signaling provides new insight into how BMP signaling can regulate LR patterning.

Keywords

Bmp4
Alk2
Alk8
Laterality
Cardiac development
Heterotaxia
Zebrafish

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1

Present address: Sars Centre for Marine Molecular Biology, University of Bergen, Thormohlensgt. 55, N-5008 Bergen, Norway.