Animal development and homeostasis depend on precise temporal and spatial intercellular signaling. Components shared between signaling pathways, generally thought to decrease specificity, paradoxically can also provide a solution to pathway coordination. Here we show that the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways share Apcdd1 as a common inhibitor and that Apcdd1 is a taxon-restricted gene with novel domains and signaling functions. Previously, we showed that Apcdd1 inhibits Wnt signaling (Shimomura et al., 2010), here we find that Apcdd1 potently inhibits BMP signaling in body axis formation and neural differentiation in chicken, frog, zebrafish. Furthermore, we find that Apcdd1 has an evolutionarily novel protein domain. Our results from experiments and modeling suggest that Apcdd1 may coordinate the outputs of two signaling pathways that are central to animal development and human disease.

动物发育和体内平衡取决于精确的时间和空间细胞间信号传导。信号通路之间共享的组件通常被认为会降低特异性，但矛盾的是，它也可以为通路协调提供解决方案。在这里，我们证明骨形态发生蛋白（BMP）和Wnt信号通路共享Apcdd1作为共同的抑制剂，并且Apcdd1是一个具有新结构域和信号功能的分类群限制基因。之前，我们发现Apcdd1抑制Wnt信号传导（Shimomura等人，2010），在这里我们发现Apcdd1有效抑制鸡、青蛙、斑马鱼体轴形成和神经分化中的BMP信号传导。此外，我们发现 Apcdd1 具有一个进化上新颖的蛋白质结构域。我们的实验和建模结果表明，Apcdd1 可能协调对动物发育和人类疾病至关重要的两条信号通路的输出。