A spatiotemporal barrier formed by Follistatin is required for left-right patterning.
A spatiotemporal barrier formed by Follistatin is required for left-right patterning.
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DOI：
10.1073/pnas.2219649120
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发表时间：
2023-06-13
影响因子：
11.1
通讯作者：
Xu, Peng-Fei
中科院分区：
文献类型：
--
作者：
Fu, Xin-Xin;Zhuo, Ding-Hao;Zhang, Ying-Jie;Li, Yun-Fei;Liu, Xiang;Xing, Yan-Yi;Huang, Ying;Wang, Yi-Fan;Cheng, Tao;Wang, Dan;Chen, Si-Han;Chen, Yi-Jian;Jiang, Guan-Nan;Lu, Fu-, I;Feng, Yu;Huang, Xiao;Ma, Jun;Liu, Wei;Bai, Ge;Xu, Peng-Fei
脊椎动物胚胎的左右模式依赖于不对称的Nodal信号从后部到前部的有序传播。这需要一个位于胚胎后尖的左右组织器（LRO）来打破双侧对称，以及一个中线屏障来阻止Nodal沿沿着方向扩散。目前的研究确定了一个新的屏障，这是建立卵泡抑素（Fst）和双边表达。这种屏障控制了不对称Nodal活动向前部的传播，以确保整个胚胎（包括前脑）的正确左右模式结果。左右（LR）不对称性如何出现在一个图案领域沿着前后轴仍然是一个未解决的问题，在发育生物学。从LR组织者发出的左偏Nodal从后向前（PA）传播，并建立整个胚胎的LR模式。然而，关于Nodal的PA扩散及其在前脑中的不对称激活的调节机制知之甚少。在这里，我们确定双边表达卵泡抑素（Fst）作为一个调节器，阻止传播的斑马鱼Nodal直系同源物Southpaw（Spaw）在右侧板中胚层（LPM），并限制Spaw传输在左侧LPM，以促进建立一个强大的LR不对称的Nodal图案。此外，Fst抑制前脑中的激活素-Nodal信号传导通路，从而防止Nodal在稍后时间从左侧LPM发出的Spaw到达之前激活。这有助于不对称节点激活沿PA轴沿着有序传播。在鸡胚和蛙胚中进一步证实了Fst的LR调节功能。总体而言，我们的研究结果表明，一个强大的LR图案出现抵消FST障碍形成沿着PA轴。
The left–right patterning of vertebrate embryos relies on an orderly propagation of the asymmetric Nodal signaling from posterior to anterior. This requires a left–right organizer (LRO) that is located at the posterior tip of the embryo to break the bilateral symmetry, as well as a midline barrier that prevents Nodal from diffusing along the left–right direction. The current study identifies a new barrier, which is set up by Follistatin (Fst) and expressed bilaterally. This barrier gates the propagation of the asymmetric Nodal activity toward the anterior to ensure a proper left–right patterning outcome throughout the entire embryo including the forebrain. How left–right (LR) asymmetry emerges in a patterning field along the anterior–posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin–Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis.
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影响因子：
64.8
作者：
Essner, JJ;Vogan, KJ;Brueckner, M
通讯作者：
Brueckner, M
影响因子：
2.7
作者：
Chocron, Sonja;Verhoeven, Manon C.;Bakkers, Jeroen
通讯作者：
Bakkers, Jeroen
DOI：
10.1073/pnas.95.16.9337
发表时间：
1998-08-04
影响因子：
11.1
作者：
Iemura, S;Yamamoto, TS;Ueno, N
通讯作者：
Ueno, N
影响因子：
4.7
作者：
Lejeune F
通讯作者：
Lejeune F
影响因子：
16.6
作者：
Juan T;Géminard C;Coutelis JB;Cerezo D;Polès S;Noselli S;Fürthauer M
通讯作者：
Fürthauer M