Chordin

InterPro Family

Chordin (from Greek χορδή, string, catgut) is a protein with a prominent role in dorsal–ventral patterning during early embryonic development. In humans it is encoded for by the CHRD gene.

Chordin was originally identified in the African clawed frog (Xenopus laevis) in the laboratory of Edward M. De Robertis as a key developmental protein that dorsalizes early vertebrate embryonic tissues. It was first hypothesized that chordin plays a role in the dorsal homeobox genes in Spemann's organizer. The chordin gene was discovered through its activation following use of gsc (goosecoid) and Xnot mRNA injections. The discoverers of chordin concluded that it is expressed in embryo regions where gsc and Xnot were also expressed, which included the prechordal plate, the notochord, and the chordoneural hinge. The expression of the gene in these regions led to the name chordin. Initial functions of chordin were thought to include recruitment of neighboring cells to assist in the forming of the axis along with mediating cell interactions for organization of tail, head, and body regions.

Chordin is a 941 amino acids long protein, whose three dimensional transmission electron microscopy structure resembles a horseshoe. A characteristic structural feature of chordin is the presence of four cysteine rich repeats, which are 58–75 residues long, each containing 10 cysteines with characteristic spacings. These repeats are homologous with domains in a number of extracellular matrix proteins, including von Willebrand factor. There are five named isoforms of this protein that are produced by alternative splicing.

CHRD is 23 exons long and has a length of 11.5 kb and is localized at 3q27. Chordin blocks BMP signaling by preventing BMP from interacting with cell surface receptors, which inhibits the formation of epidermis and promoting the formation of neural tissue. Chordin specifically inhibits BMP 2, 4, 7. This is significant because when only noggin is deficient there are mild defects but the head still forms. Noggin has been shown to have overlap at the midgastrula in its expression with chordin. As the streak evolves to a node and axial mesoderm, the chordin mRNA is still expressed. This evidence suggests a patterning role of chordin during the early embryo stages. In developing mice that are deficient in both chordin and noggin, the head is nearly absent. Chordin is also involved in avian gastrulation and may also play a role in organogenesis.