Hsu D R, Economides A N, Wang X, Eimon P M, Harland R M
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Mol Cell. 1998 Apr;1(5):673-83. doi: 10.1016/s1097-2765(00)80067-2.
Using a Xenopus expression-cloning screen, we have isolated Gremlin, a novel antagonist of bone morphogenetic protein (BMP) signaling that is expressed in the neural crest. Gremlin belongs to a novel gene family that includes the head-inducing factor Cerberus and the tumor suppressor DAN. We show that all family members are secreted proteins and that they act as BMP antagonists in embryonic explants. We also provide support for the model that Gremlin, Cerberus, and DAN block BMP signaling by binding BMPs, preventing them from interacting with their receptors. In addition, Cerberus alone blocks signaling by Activin- and Nodal-like members of the TGF beta superfamily. Therefore, we propose that Gremlin, Cerberus, and DAN control diverse processes in growth and development by selectively antagonizing the activities of different subsets of the TGF beta ligands.
通过非洲爪蟾表达克隆筛选，我们分离出了Gremlin，它是一种在神经嵴中表达的骨形态发生蛋白（BMP）信号通路的新型拮抗剂。Gremlin属于一个新的基因家族，该家族包括头部诱导因子Cerberus和肿瘤抑制因子DAN。我们发现所有家族成员都是分泌蛋白，并且它们在胚胎外植体中作为BMP拮抗剂发挥作用。我们还为以下模型提供了支持：Gremlin、Cerberus和DAN通过结合BMP来阻断BMP信号，从而阻止它们与受体相互作用。此外，单独的Cerberus可阻断转化生长因子β（TGFβ）超家族中激活素和Nodal样成员的信号传导。因此，我们提出Gremlin、Cerberus和DAN通过选择性拮抗TGFβ配体不同亚群的活性来控制生长和发育中的多种过程。
