Taylor Elias, Corsini Megan, Heyland Andreas
College of Biological Sciences, University of Guelph, Integrative Biology, Guelph, ON, N1G-2W1, Canada.
Evodevo. 2024 Aug 7;15(1):10. doi: 10.1186/s13227-024-00226-2.
Thyroid hormones are crucial regulators of metamorphosis and development in bilaterians, particularly in chordate deuterostomes. Recent evidence suggests a role for thyroid hormone signaling, principally via 3,5,3',5'-Tetraiodo-L-thyronine (T4), in the regulation of metamorphosis, programmed cell death and skeletogenesis in echinoids (sea urchins and sand dollars) and sea stars. Here, we test whether TH signaling in skeletogenesis is a shared trait of Echinozoa (Echinoida and Holothouroida) and Asterozoa (Ophiourida and Asteroida). We demonstrate dramatic acceleration of skeletogenesis after TH treatment in three classes of echinoderms: sea urchins, sea stars, and brittle stars (echinoids, asteroids, and ophiuroids). Fluorescently labeled thyroid hormone analogues reveal thyroid hormone binding to cells proximal to regions of skeletogenesis in the gut and juvenile rudiment. We also identify, for the first time, a potential source of thyroxine during gastrulation in sea urchin embryos. Thyroxine-positive cells are present in tip of the archenteron. In addition, we detect thyroid hormone binding to the cell membrane and nucleus during metamorphic development in echinoderms. Immunohistochemistry of phosphorylated MAPK in the presence and absence of TH-binding inhibitors suggests that THs may act via phosphorylation of MAPK (ERK1/2) to accelerate initiation of skeletogenesis in the three echinoderm groups. Together, these results indicate that TH regulation of mesenchyme cell activity via integrin-mediated MAPK signaling may be a conserved mechanism for the regulation of skeletogenesis in echinoderm development. In addition, TH action via a nuclear thyroid hormone receptor may regulate metamorphic development. Our findings shed light on potentially ancient pathways of thyroid hormone activity in echinoids, ophiuroids, and asteroids, or on a signaling system that has been repeatedly co-opted to coordinate metamorphic development in bilaterians.
甲状腺激素是两侧对称动物变态发育和生长发育的关键调节因子，尤其是在脊索动物后口动物中。最近的证据表明，甲状腺激素信号传导，主要通过3,5,3',5'-四碘-L-甲状腺原氨酸（T4），在棘皮动物（海胆和沙钱）和海星的变态发育、程序性细胞死亡和骨骼生成调节中发挥作用。在这里，我们测试甲状腺激素信号传导在骨骼生成中是否是海胆纲（海胆目和海参纲）和海星纲（蛇尾目和海星目）的共同特征。我们证明，在三类棘皮动物：海胆、海星和蛇尾（海胆类、海星类和蛇尾类）中，甲状腺激素处理后骨骼生成显著加速。荧光标记的甲状腺激素类似物显示甲状腺激素与肠道和幼体原基中骨骼生成区域附近的细胞结合。我们还首次确定了海胆胚胎原肠胚形成过程中甲状腺素的潜在来源。甲状腺素阳性细胞存在于原肠的顶端。此外，我们在棘皮动物变态发育过程中检测到甲状腺激素与细胞膜和细胞核结合。在存在和不存在甲状腺激素结合抑制剂的情况下，对磷酸化丝裂原活化蛋白激酶进行免疫组织化学分析表明，甲状腺激素可能通过丝裂原活化蛋白激酶（ERK1/2）的磷酸化作用来加速这三类棘皮动物骨骼生成的启动。总之，这些结果表明，甲状腺激素通过整合素介导的丝裂原活化蛋白激酶信号传导调节间充质细胞活性，可能是棘皮动物发育过程中骨骼生成调节的一种保守机制。此外，甲状腺激素通过核甲状腺激素受体的作用可能调节变态发育。我们的研究结果揭示了海胆类、蛇尾类和海星类中甲状腺激素活性潜在的古老途径，或者揭示了一个被反复利用以协调两侧对称动物变态发育的信号系统。
