Synergistic interaction between Gdf1 and Nodal during anterior axis development
Synergistic interaction between Gdf1 and Nodal during anterior axis development
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DOI：
10.1016/j.ydbio.2006.02.002
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发表时间：
2006-05-15
影响因子：
2.7
通讯作者：
Ibanez, Carlos F.
中科院分区：
文献类型：
--
作者：
Andersson, Olov;Reissmann, Eva;Ibanez, Carlos F.
生长和分化因子1（GDF-1）与小鼠胚胎的左右模式有关，但没有其他已知的功能。在这里，我们展示了Gdf 1和Nodal在前轴发育过程中的遗传相互作用。Gdf1（-/-）; Nodal（+/-）突变体显示出Gdf 1（-/-）或Nodal（+/-）单突变体中不存在的几种异常，包括脊索和前索板的缺失，以及前肠的畸形;分别与前头和鳃弓的发育有关的组织中心。与这些缺陷相一致，Gdf 1（-/-）;Nodal（+/-）突变胚胎显示出许多轴向中线异常，包括前脑无裂、前头部截短、唇裂、融合的鼻腔以及缺乏颌骨和舌头。在单一突变体中不存在这些缺陷表明节点和GDF-1在节点中的协同相互作用，从中产生脊索、前索板和前肠内胚层的轴向中内胚层起源，并且这两种因子共表达。这一观点得到了支持的FoxA 2和goosecoid在前原始条纹的双突变胚胎的严重下调。与侧板中胚层不同的是，节点中Nodal的表达不依赖于GDF-1，表明这两个因子平行地控制中内胚层前体的发育。受体重建实验表明，GDF-1与Nodal一样，可以通过I型受体ALK 4和ALK 7发出信号。然而，复合突变体的分析表明，ALK 4，而不是ALK 7，负责GDF-1和Nodal在前轴发育过程中的作用。这些结果表明，GDF-1和Nodal会聚在前原条中的ALK 4上，以控制正常前脑和鳃弓发育所必需的组织中心的形成。(c)2006年爱思唯尔公司All rights reserved.
Growth and Differentiation Factor 1 (GDF-1) has been implicated in left-right patterning of the mouse embryo but has no other known function. Here, we demonstrate a genetic interaction between Gdf1 and Nodal during anterior axis development. Gdf1(-/-);Nodal(+/-) mutants displayed several abnormalities that were not present in either Gdf1(-/-) or Nodal(+/-) single mutants, including absence of notochord and prechordal plate, and malformation of the foregut; organizing centers implicated in the development of the anterior head and branchial arches, respectively. Consistent with these deficits, Gdf1(-/-);Nodal(+/-) mutant embryos displayed a number of axial midline abnormalities, including holoprosencephaly, anterior head truncation, cleft lip, fused nasal cavity, and lack of jaws and tongue. The absence of these defects in single mutants indicated a synergistic interaction between Nodal and GDF-1 in the node, from which the axial mesendoderm that gives rise to the notochord, prechordal plate, and foregut endoderm originates, and where the two factors are co-expressed. This notion was supported by a severe downregulation of FoxA2 and goosecoid in the anterior primitive streak of double mutant embryos. Unlike that in the lateral plate mesoderm, Nodal expression in the node was independent of GDF-1, indicating that both factors act in parallel to control the development of mesendodermal precursors. Receptor reconstitution experiments indicated that GDF-1, like Nodal, can signal through the type I receptors ALK4 and ALK7. However, analysis of compound mutants indicated that ALK4, but not ALK7, was responsible for the effects of GDF-1 and Nodal during anterior axis development. These results indicate that GDF-1 and Nodal converge on ALK4 in the anterior primitive streak to control the formation of organizing centers that are necessary for normal forebrain and branchial arch development. (c) 2006 Elsevier Inc. All rights reserved.