Coco
Coco (COCO/DAND5) is a secreted Cerberus/DAN-family regulator that controls embryonic cell fate by inhibiting BMP, TGFβ/Activin-Nodal, and Wnt signaling[1]. Mechanistically, maternal Coco regulates germ-layer specification through TGFβ signaling inhibition, while Cerl2/Coco controls left-right patterning by restricting and terminating Nodal activity in the mouse node[2][3]. Compared with related extracellular antagonists such as Noggin, Chordin, and Follistatin, Coco shows ligand-dependent activity because it inhibits BMP/Activin/Nodal but enhances TGFβ1-ALK5 receptor interaction[4]. In disease models, Coco reactivates dormant breast cancer cells at lung metastatic sites by blocking lung-derived BMP ligands[5]. For experimental applications, exogenous COCO inhibits endothelial sprouting, migration, proliferation, retinal vascularization, and pathological ocular neovascularization[6].
References:
- [1]. Bell E, et al. Cell fate specification and competence by Coco, a maternal BMP, TGFbeta and Wnt inhibitor. Development. 2003 Apr;130(7):1381-9. [Content Brief]
- [2]. Bates TJ, et al. Coco regulates dorsoventral specification of germ layers via inhibition of TGFβ signalling. Development. 2013 Oct;140(20):4177-81. [Content Brief]
- [3]. Inácio JM, et al. The dynamic right-to-left translocation of Cerl2 is involved in the regulation and termination of Nodal activity in the mouse node. PLoS One. 2013;8(3):e60406. [Content Brief]
- [4]. Deglincerti A, et al. Coco is a dual activity modulator of TGFβ signaling. Development. 2015 Aug 1;142(15):2678-85. [Content Brief]
- [5]. Gao H, et al. The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell. 2012 Aug 17;150(4):764-79. [Content Brief]
- [6]. Popovic N, et al. COCO/DAND5 inhibits developmental and pathological ocular angiogenesis. EMBO Mol Med. 2021 Mar 5;13(3):e12005. [Content Brief]
