BMP inhibition by DAN in Hensen's node is a critical step for the establishment of left-right asymmetry in the chick embryo
BMP inhibition by DAN in Hensen's node is a critical step for the establishment of left-right asymmetry in the chick embryo
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DOI：
10.1016/j.ydbio.2011.12.015
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发表时间：
2012-03-01
影响因子：
2.7
通讯作者：
Yokouchi, Yuji
中科院分区：
文献类型：
--
作者：
Katsu, Kenjiro;Tokumori, Daisuke;Yokouchi, Yuji
在脊椎动物胚胎左右(L-R)轴的形成过程中，Nodal在结节中表达，并在L-R信息的传递中起着中心作用。骨形态发生蛋白(BMP)信号在维持结节周围基因表达方面也起着重要作用。Cerberus/Dan家族的几个成员通过调节转化生长因子-β家族的活性来作用于L-R模式。我们在这里证明了鸡丹在L-R轴的形成中起着关键作用。在左手Shh表达后不久，在侧板中胚层(LPM)出现不对称表达基因之前，鸡丹在结节的左侧表达。体外实验表明，丹抑制BMP信号转导，但不抑制结节信号转导。Shh对DAN的表达有正向调节作用，而BMP4有负向调节作用。利用过表达和RNA干扰介导的基因敲除策略，我们证明了DAN对于Nodal在LPM中的表达和Lefty-1在脊索中的表达是必不可少的。在结周区域，Dan和Nodal的表达是相互独立的。DAN对结节的上调需要结节信号，提示DAN可能与Node协同作用。我们的数据表明，DAN通过抑制节点周围的骨形态发生蛋白信号，在L-R轴的建立中发挥重要作用。(C)2012 Elsevier Inc.保留所有权利。
During left-right (L-R) axis formation, Nodal is expressed in the node and has a central role in the transfer of L-R information in the vertebrate embryo. Bone morphogenetic protein (BMP) signaling also has an important role for maintenance of gene expression around the node. Several members of the Cerberus/Dan family act on L-R patterning by regulating activity of the transforming growth factor-beta (TGF-beta) family. We demonstrate here that chicken Dan plays a critical role in L-R axis formation. Chicken Dan is expressed in the left side of the node shortly after left-handed Shh expression and before the appearance of asymmetrically expressed genes in the lateral plate mesoderm (LPM). In vitro experiments revealed that DAN inhibited BMP signaling but not NODAL signaling. SHH had a positive regulatory effect on Dan expression while BMP4 had a negative effect. Using overexpression and RNA interference-mediated knockdown strategies, we demonstrate that Dan is indispensable for Nodal expression in the LPM and for Lefty-1 expression in the notochord. In the perinodal region, expression of Dan and Nodal was independent of each other. Nodal up-regulation by DAN required NODAL signaling, suggesting that DAN might act synergistically with NODAL Our data indicate that Dan plays an essential role in the establishment of the L-R axis by inhibiting BMP signaling around the node. (C) 2012 Elsevier Inc. All rights reserved.