Chordin,
Chordin-like 1, and
Chordin-like 2 are secreted
bone morphogenetic protein (BMP) antagonists with highly conserved
Chordin-like
cysteine-rich domains. Recently, Brorin and Brorin-like have been identified as new
Chordin-like BMP antagonists. A
Chordin ortholog, Short gastrulation, has been identified in Drosophila, a protostome, but not other orthologs. By contrast,
Chordin,
Chordin-like 1, and
Chordin-like 2 have been identified in Ciona intestinalis, the closest living relatives of the vertebrates, but Brorin and Brorin-like have not. However, all these genes have been identified in most vertebrates. These results indicate that
Chordin,
Chordin-like 1, and
Chordin-like 2 were generated early in the metazoan lineage. Later on, Brorin and Brorin-like were potentially generated by a genome duplication event in early vertebrate evolution. All four
cysteine-rich domains of
Chordin are essential for the regulation of its action. However,
Chordin-like 1,
Chordin-like 2, Brorin, and Brorin-like contain only two or three
cysteine-rich domains. Although their mechanisms of action remain unclear, they might be distinct from that of
Chordin. The expression profiles of these genes in mice and zebrafish indicate unique roles at embryonic and postnatal stages. Mutant/knockdown mouse and zebrafish phenotypes indicate roles in morphogenesis during gastrulation, dorsoventral axis formation, ear, pharyngeal, and neural development, and venous and arterial patterning. Aberrant
Chordin expression might result in
hereditary diseases and
cancer. In addition, altered serum
Chordin and
Chordin-like 1 levels are also observed in non-
hereditary diseases. Together, these results indicate pathophysiological roles.