Reciprocal Signaling between the Ectoderm and a Mesendodermal Left-Right Organizer Directs Left-Right Determination in the Sea Urchin Embryo

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.

在棘皮动物发育过程中，右侧Nodal（nodal）基因的表达对于左侧幼体原基的定位具有关键调控作用，但将Nodal表达限制在右侧的具体机制仍未阐明。本研究证实，海胆胚胎左右不对称性的建立依赖于外胚层与位于内中胚层的左右组织者之间的双向信号交互。成纤维细胞生长因子/细胞外调节蛋白激酶（FGF/ERK）与骨形态发生蛋白2/4（BMP2/4）信号通路是该左右组织者中启动Nodal表达所必需的，而德尔塔/Notch（Delta/Notch）信号通路则可抑制原肠左侧该组织者的形成。此外，本研究发现氢钾ATP酶（H+/K+-ATPase）在Notch信号通路中Notch蛋白S3切割的上游环节发挥关键调控功能。本研究结果明确了非脊索动物后口动物胚胎发育过程中，介导左右不对称性启动、限制与传播的多个新型调控因子与关键早期步骤，并揭示了氢钾ATP酶与Notch信号通路之间的功能关联。