Michael Sars Centre, University of Bergen, Thormøhlensgate 55, 5008, Bergen, Norway.
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307, Dresden, Germany.
BMC Biol. 2024 Sep 19;22(1):212. doi: 10.1186/s12915-024-01988-w.
Wnt signaling pathways play crucial roles in animal development. They establish embryonic axes, specify cell fates, and regulate tissue morphogenesis from the early embryo to organogenesis. It is becoming increasingly recognized that these distinct developmental outcomes depend upon dynamic interactions between multiple ligands, receptors, antagonists, and other pathway modulators, consolidating the view that a combinatorial "code" controls the output of Wnt signaling. However, due to the lack of comprehensive analyses of Wnt components in several animal groups, it remains unclear if specific combinations always give rise to specific outcomes, and if these combinatorial patterns are conserved throughout evolution.
In this work, we investigate the combinatorial expression of Wnt signaling components during the axial patterning of the brachiopod Terebratalia transversa. We find that T. transversa has a conserved repertoire of ligands, receptors, and antagonists. These genes are expressed throughout embryogenesis but undergo significant upregulation during axial elongation. At this stage, Frizzled domains occupy broad regions across the body while Wnt domains are narrower and distributed in partially overlapping patches; antagonists are mostly restricted to the anterior end. Based on their combinatorial expression, we identify a series of unique transcriptional subregions along the anteroposterior axis that coincide with the different morphological subdivisions of the brachiopod larval body. When comparing these data across the animal phylogeny, we find that the expression of Frizzled genes is relatively conserved, whereas the expression of Wnt genes is more variable.
Our results suggest that the differential activation of Wnt signaling pathways may play a role in regionalizing the anteroposterior axis of brachiopod larvae. More generally, our analyses suggest that changes in the receptor context of Wnt ligands may act as a mechanism for the evolution and diversification of the metazoan body axis.
Wnt 信号通路在动物发育中起着至关重要的作用。它们建立胚胎轴，指定细胞命运，并调节从早期胚胎到器官发生的组织形态发生。人们越来越认识到，这些不同的发育结果取决于多个配体、受体、拮抗剂和其他途径调节剂之间的动态相互作用，这巩固了这样一种观点，即组合“密码”控制着 Wnt 信号的输出。然而，由于缺乏对几个动物群体中 Wnt 成分的全面分析，目前尚不清楚特定的组合是否总是产生特定的结果，以及这些组合模式是否在进化过程中保持保守。
在这项工作中，我们研究了腕足动物 Terebratalia transversa 轴向模式形成过程中 Wnt 信号成分的组合表达。我们发现 T. transversa 具有保守的配体、受体和拮抗剂 repertoire。这些基因在整个胚胎发生过程中表达，但在轴向伸长过程中显著上调。在这个阶段，Frizzled 结构域占据身体的广泛区域，而 Wnt 结构域较窄，分布在部分重叠的斑块中；拮抗剂主要局限于前端。根据它们的组合表达，我们在沿前后轴的一系列独特的转录亚区中识别出与腕足动物幼虫身体不同形态细分相对应的亚区。当将这些数据在动物系统发育中进行比较时，我们发现 Frizzled 基因的表达相对保守，而 Wnt 基因的表达则更为可变。
我们的结果表明，Wnt 信号通路的差异激活可能在腕足动物幼虫前后轴的区域化中发挥作用。更一般地说，我们的分析表明，Wnt 配体的受体背景的变化可能是后生动物体轴进化和多样化的一种机制。
