A gene encoding a novel secreted protein in mice and humans was identified, and named Neucrin. Mouse Neucrin consists of 343 amino acids with a cysteine-rich domain in its carboxyl terminal region. The positions of 10 cysteine residues in the cysteine-rich domain are similar to those of Dickkopfs (Dkks), secreted Writ antagonists. However, whereas Dkks have two cysteine-rich domains, Neucrin has only one. Neucrin as well as Dkks bound to LDL receptor-related protein 6 and inhibited the stabilization of cytosolic beta-catenin, indicating that Neucrin is an antagonist of canonical Wnt signaling. Mouse Neucrin expression was not detected in any major tissues in the adult, but was detected in developing neural tissues, including the brain and spinal cord. The expression pattern of Neucrin is distinct from that of any Dkk. Neucrin is a unique secreted Wnt antagonist that is predominantly expressed in developing neural tissues. (C) 2009 Elsevier Inc. All rights reserved.