Man1, an inner nuclear membrane protein, regulates left–right axis formation by controlling nodal signaling in a node‐independent manner
Copyright policy )Man1, an inner nuclear membrane protein, regulates left–right axis formation by controlling nodal signaling in a node‐independent manner
AbstractMan1, an inner nuclear membrane protein, regulates transforming growth factor β signaling by interacting with receptor‐associated Smads. In Man1‐deficient (Man1Δ/Δ) embryos, vascular remodeling is perturbed by misregulation of Smad activity. Here, we show that Man1Δ/Δ embryos exhibit abnormal heart morphogenesis including the looping abnormality. We searched for the molecular basis underlying the heart abnormalities and found that the left side‐specific genes responsible for left–right (LR) asymmetry, Nodal, Lefty2, and Pitx2, were expressed bilaterally in the lateral plate mesoderm and that their expression was enhanced significantly in mutants. Notably, Lefty1, a marker for the midline barrier, was maintained in Man1Δ/Δ mutants. Crossing Man1Δ/+ with Nodal hypomorphs (Nodalneo/+), in which Nodal signaling in the node is disrupted, to generate double homozygous embryos (Man1Δ/Δ; Nodalneo/neo) revealed that the bilateral Nodal was retained in Man1Δ/Δ; Nodalneo/neo embryos. These results suggest that Man1 regulates LR asymmetry by controlling Nodal signaling in a node‐independent manner. Developmental Dynamics 237:3565–3576, 2008. © 2008 Wiley‐Liss, Inc.
- Akita University Japan
Mice, Knockout, Nodal Protein, Myocardium, Bone Morphogenetic Protein 2, Gene Expression Regulation, Developmental, Membrane Proteins, Nuclear Proteins, Heart, Body Fluids, DNA-Binding Proteins, Mice, Microscopy, Electron, Scanning, Animals, Body Patterning, Signal Transduction
Mice, Knockout, Nodal Protein, Myocardium, Bone Morphogenetic Protein 2, Gene Expression Regulation, Developmental, Membrane Proteins, Nuclear Proteins, Heart, Body Fluids, DNA-Binding Proteins, Mice, Microscopy, Electron, Scanning, Animals, Body Patterning, Signal Transduction
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