PDF(Pubmed)
Abstract：
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.
摘要：
左右（LR）不对称性如何在沿前后轴的图案化场中出现仍然是发育生物学中尚未解决的问题。从LR组织者发出的左偏Nodal从后向前（PA）传播，并建立了整个胚胎的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。这里,我们确定了双侧表达的Follistatin（Fst）是阻止斑马鱼Nodal直系同源Southpaw（Spaw）在右侧板中胚层（LPM）中繁殖的调节剂，并限制左侧LPM中的Spaw传输，以促进建立稳健的LR非对称节点图案。此外,Fst抑制前脑中的Activin-Nodal信号通路，从而在到达之前阻止Nodal激活，在稍后的时间，从左LPM发出的Spaw。这有助于非对称Nodal激活沿PA轴的有序传播。Fst的LR调节功能在鸡和青蛙胚胎中得到进一步证实。总的来说,我们的结果表明，通过抵消沿PA轴形成的Fst屏障，可以产生强大的LR图案。
