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 Left-Right Axis Formation by Controlling Nodal Signaling in a Node-Independent Manner
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DOI：
10.1002/dvdy.21663
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发表时间：
2008-12-01
影响因子：
2.5
通讯作者：
Osada, Shin-Ichi
中科院分区：
文献类型：
--
作者：
Ishimura, Akihiko;Chida, Shinsuke;Osada, Shin-Ichi
Man 1是一种内核膜蛋白，通过与受体相关Smads相互作用调节转化生长因子β信号传导。在Man 1缺陷（Man 1（Delta/Delta））胚胎中，血管重塑受到Smad活性失调的干扰。在这里，我们表明，曼1（三角洲/三角洲）胚胎表现出异常的心脏形态发生，包括循环异常。我们寻找了心脏异常的分子基础，发现负责左右（LR）不对称的左侧特异性基因，Nodal，Lefty 2和Pitx 2，在侧板中胚层中双侧表达，并且它们的表达在突变体中显著增强。值得注意的是，中线屏障的标记物Leftyl在Manl（Delta/Delta）突变体中得以维持。将Man 1（Delta/+）与Nodal亚型（Nodal（neo/+））杂交以产生双纯合胚胎（Man 1（Delta/Delta）; Nodal（neo/neo）），其中节点中的Nodal信号被破坏，揭示了双侧Nodal保留在Man 1（Delta/Delta）; Nodal（neo/neo）胚胎中。这些结果表明，Man 1调节LR的不对称性，通过控制Nodal信号在一个节点独立的方式。发展动力学237：3565-3576，2008年。(C)2008 Wiley-Liss，Inc.
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, Leftyl, 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. Developmental Dynamics 237: 3565-3576, 2008. (C) 2008 Wiley-Liss, Inc.