Recombinant Mouse Cerberus 1 Protein, CF

Cerberus 1, also called DAND4, is a member of the DAN domain family of BMP antagonists that includes DAN (DAND1), Gremlin/Drm (DAND2), PRDC (Protein Related to Dan and Cerberus; DAND3), and COCO/Dante (DAND5). DAN family members contain a cysteine-knot domain that is homologous to that found in other TGF-beta superfamily ligands (1, 2). Mature mouse Cerberus 1 shares 40%, 29%, and 66% amino acid (aa) sequence identity with chick, Xenopus, and human Cerberus 1, respectively. Within the cysteine-knot domain, it shares 24% - 37% aa sequence identity with mouse DAN, Gremlin, PRDC, and COCO. Cerberus 1 is a secreted 38 kDa glycoprotein that forms disulfide-linked homodimers (3). Cerberus-S, which is generated by proteolysis in Xenopus, is a short version of the molecule and includes the C-terminal cysteine-knot domain (4). At the onset of gastrulation, Cerberus 1 is transiently expressed in anterior endodermal structures in response to Nodal and Shh (3, 5 - 9). Cerberus 1 binds BMP-4 and Nodal and inhibits their activities. Xenopus Cerberus has also been shown to bind Xenopus Wnt8. These inhibitory functions of Cerberus favor mesodermal development in the anterior region of the gastrula and suppresses posterior mesodermal differentiation (3, 4, 6, 8, 10 - 12). In chick and Xenopus, Cerberus 1 also regulates, but is not required for embryonic left-right polarization, neurulation, and head and heart induction (4 - 8, 13).