Man1, an inner nuclear membrane protein, regulates left-right axis formation by controlling nodal signaling in a node-independent manner.
Man1, an inner nuclear membrane protein, regulates transforming growth factor beta signaling by interacting with receptor-associated Smads. In Man1-deficient (Man1(Delta/Delta)) embryos, vascular remodeling is perturbed by misregulation of Smad activity. Here, we show that Man1(Delta/Delta) 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 Man1(Delta/Delta) mutants. Crossing Man1(Delta/+) with Nodal hypomorphs (Nodal(neo/+)), in which Nodal signaling in the node is disrupted, to generate double homozygous embryos (Man1(Delta/Delta); Nodal(neo/neo)) revealed that the bilateral Nodal was retained in Man1(Delta/Delta); Nodal(neo/neo) embryos. These results suggest that Man1 regulates LR asymmetry by controlling Nodal signaling in a node-independent manner.
Ishimura
Akihiko
A
The 21st Century Center of Excellence (COE) Program, Akita University, Akita, Japan.
Chida
Shinsuke
S
Osada
Shin-Ichi
S
D000818:Animals; D001826:Body Fluids; D019521:Body Patterning; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000378:metabolism; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D004268:DNA-Binding Proteins; C515012:Man1 protein, mouse; D008565:Membrane Proteins; D055457:Nodal Protein; D009687:Nuclear Proteins