Fig. 4. CR-containing proteins and their possible roles in positive feedback and spatial bi-stability. (A) The domain structures of several BMP-binding proteins. Sog is a secreted (signal peptide, SP, yellow) protein that contains BMP-binding modules [cysteine-rich motifs (CRs), green], whereas Cv-2, and its vertebrate homologs (not shown), and other related vertebrate proteins, such as Kielin or KCP, contain both CR domains and a von Willebrand Factor D (VWFD) motif (red) that may promote cell surface localization. The CRIM1 protein also contains CR domains but instead of a VWFD, it contains an insulin-like growth factor binding protein domain (IGFBP), a transmembrane domain (TM) that is likely to anchor it to the cell surface, and a small cytoplasmic tail (Cyto). (B) Position (or BMP) versus BMP-bound receptor for on/off equilibrium (dotted line) and positive feedback induced bi-stability (solid line). In general the distribution of morphogen is non-linear in x [BMP=f(x)]; however, in this case, the extracellular gradient of BMP is linear in position (i.e. BMP^*x). As the level of BMP increases, the level of BMP-bound receptor follows the on/off equilibrium solution until it reaches a limit point (LP) where the lower equilibrium solution ceases to exist. For levels of BMP above this point, the level of BMP-bound receptor approaches the upper stable branch.