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Determination of the vertebrate left-right body axis during embryogenesis results in asymmetric development and placement of most inner organs. Although the asymmetric Nodal cascade is conserved in all vertebrates, the mechanism of symmetry breakage has remained controversial. In mammalian and fish embryos, a cilia-driven leftward flow of extracellular(More)
Vertebrate organ laterality is manifested by the asymmetric morphogenesis and placement of inner organs. Asymmetric induction of the Nodal signaling cascade in the left lateral plate mesoderm (LPM) precedes and is essential for asymmetric organ morphogenesis. While the Nodal cascade is highly conserved, symmetry breakage is considered to vary between the(More)
Generation of laterality depends on a pathway which involves the asymmetrically expressed genes nodal, Ebaf, Leftb, and Pitx2. In mouse, node monocilia are required upstream of the nodal cascade. In chick and frog, gap junctions are essential prior to node/organizer formation. It was hypothesized that differential activity of ion channels gives rise to(More)
During vertebrate embryogenesis, a left-right axis is established. The heart, associated vessels and inner organs adopt asymmetric spatial arrangements and morphologies. Secreted growth factors of the TGF-beta family, including nodal, lefty-1 and lefty-2, play crucial roles in establishing left-right asymmetries [1] [2] [3]. In zebrafish, nodal signalling(More)
During vertebrate left-right development the homeobox gene Pitx2 serves as a mediator between transient nodal signaling in the left lateral plate mesoderm (l-LPM) and asymmetric organ morphogenesis. Misexpression of Pitx2 in chick and frog led to alteration of organ situs. Here we report the presence of different Pitx2 isoforms in mouse and frog. Pitx2c but(More)
In vertebrates, laterality - the asymmetric placement of the viscera including organs of the gastrointestinal system, heart and lungs - is under the genetic control of a conserved signaling pathway in the left lateral plate mesoderm (LPM). A key feature of this pathway, shared by embryos of all non-avian vertebrate classes analyzed to date (e.g. fish,(More)
The mammalian node, the functional equivalent of the frog dorsal blastoporal lip (Spemann's organizer), was originally described by Viktor Hensen in 1876 in the rabbit embryo as a mass of cells at the anterior end of the primitive streak. Today, the term "node" is commonly used to describe a bilaminar epithelial groove presenting itself as an indentation or(More)
Vertebrate laterality, which is manifested by asymmetrically placed organs [1], depends on asymmetric activation of the Nodal signaling cascade in the left lateral plate mesoderm [2]. In fish, amphibians, and mammals, a cilia-driven leftward flow of extracellular fluid acts upstream of the Nodal cascade [3-6]. The direct target of flow has remained elusive.(More)
Most vertebrate embryos break symmetry by a cilia-driven leftward flow during neurulation. In the frog Xenopus asymmetric expression of the ion pump ATP4a was reported at the 4-cell stage. The "ion-flux" model postulates that symmetry is broken flow-independently through an ATP4-generated asymmetric voltage gradient that drives serotonin through gap(More)
The invariant asymmetric placement of thoracic and abdominal organs in the vertebrates is controlled by the left-asymmetric activity of the Nodal signaling cascade during embryogenesis. In the mouse embryo asymmetric induction of nodal is thought to be dependent on functional monocilia on the ventral node cells and on the Pkd2 gene, which encodes the(More)