Zebrafish Bmp4 regulates left-right asymmetry at two distinct developmental time points.
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.
Chocron
Sonja
S
Cardiac Development and Genetics Group, Hubrecht Laboratory, Uppsalalaan 8, Utrecht, The Netherlands.
Verhoeven
Manon C
MC
Rentzsch
Fabian
F
Hammerschmidt
Matthias
M
Bakkers
Jeroen
J
D030201:Activin Receptors, Type I / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007839:Functional Laterality / Q000235:genetics; D006321:Heart / Q000196:embryology; D015398:Signal Transduction / Q000235:genetics; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D029961:Zebrafish Proteins; C525813:bmp4 protein, zebrafish; D030201:Activin Receptors, Type I; C424203:acvr1l protein, zebrafish