Reciprocal signaling between the ectoderm and a mesendodermal left-right organizer directs left-right determination in the sea urchin embryo.
Reciprocal signaling between the ectoderm and a mesendodermal left-right organizer directs left-right determination in the sea urchin embryo.
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DOI：
10.1371/journal.pgen.1003121
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Lepage T
中科院分区：
文献类型：
--
作者：
Bessodes N;Haillot E;Duboc V;Röttinger E;Lahaye F;Lepage T
在棘皮动物发育过程中，nodal在右侧的表达对左侧原基的定位起着至关重要的作用，但限制nodal在右侧表达的机制尚不清楚。在这里，我们表明，建立左右不对称的海胆胚胎依赖于相互之间的信号外胚层和位于内中胚层的左右组织者。FGF/ERK和BMP 2/4信号传导需要启动该组织者中的节点表达，而Delta/Notch信号传导需要抑制该组织者在原肠左侧的形成。此外，我们报告说，H+/K+-ATP酶是至关重要的Notch信号通路上游的S3切割的Notch。我们的研究结果确定了几个新的球员和关键的早期步骤负责启动，限制和传播的左右不对称的胚胎发育过程中的非脊索动物后口，并揭示了H+/K+-ATP酶和Notch信号通路之间的功能联系。身体左右两侧的不对称性是大多数两侧对称动物的基本特征，如果不能建立这些不对称性，可能会导致人类的病理性疾病。左右不对称性是在早期发育过程中通过胚胎中起左右轴组织者作用的离散区域中的信号通路的不对称活性建立的。虽然这个信号通路的作用似乎是保守的脊椎动物，是否在最初的对称性破坏和建立的左，右组织者参与的机制也是保守的仍然是一个悬而未决的问题。我们报告说，左右轴决定在海胆胚胎也依赖于活动的左右组织者位于肠道内的海胆胚胎。我们还报告了一个意想不到的发现，即H+/K+-ATP酶的活性是Notch受体激活的关键。因此，我们的研究结果开辟了分析调节海胆胚胎侧化建立的分子途径的途径，并揭示了左右不对称的两个重要参与者之间的功能联系。
During echinoderm development, expression of nodal on the right side plays a crucial role in positioning of the rudiment on the left side, but the mechanisms that restrict nodal expression to the right side are not known. Here we show that establishment of left-right asymmetry in the sea urchin embryo relies on reciprocal signaling between the ectoderm and a left-right organizer located in the endomesoderm. FGF/ERK and BMP2/4 signaling are required to initiate nodal expression in this organizer, while Delta/Notch signaling is required to suppress formation of this organizer on the left side of the archenteron. Furthermore, we report that the H+/K+-ATPase is critically required in the Notch signaling pathway upstream of the S3 cleavage of Notch. Our results identify several novel players and key early steps responsible for initiation, restriction, and propagation of left-right asymmetry during embryogenesis of a non-chordate deuterostome and uncover a functional link between the H+/K+-ATPase and the Notch signaling pathway. Asymmetries between the left and the right sides of the body are an essential feature of most bilaterian animals, and failure to establish these asymmetries can result in pathological disorders in humans. Left-right asymmetries are established during early development by the asymmetric activity of a signaling pathway in a discrete region of the embryo that plays the role of a left-right axis organizer. Although the role of this signaling pathway appears to be conserved among vertebrates, whether the mechanisms involved in the initial breaking of the symmetry and in the establishment of the left-right organizer are also conserved remains an open question. We report that left-right axis determination in the sea urchin embryo also relies on the activity of a left-right organizer located within the gut of the sea urchin embryo. We also report the unexpected finding that the activity of the H+/K+-ATPase, a previously known but enigmatic player in this pathway, is critically required for activation of the Notch receptor. Our results therefore open the way to analysis of the molecular pathway that regulates establishment of laterality in the sea urchin embryo and uncover a functional link between two essential players of left-right asymmetry.
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