Recombinant Mouse Draxin Protein

Draxin (Dorsal repulsive axon guidance protein) also called neucrin (neural tissue-specific cysteine-rich protein) is a secreted, 58 kDa, presumably glycosylated member of the draxin family of repulsive guidance proteins (1 ‑ 5). In mammals, it is expressed in developing neurons (axons), astroglia, and likely cells of the developing somite (1 ‑ 3). Its expression appears to be limited to the brain and spinal cord (2, 4). Mouse Draxin mRNA encodes 343 amino acids (aa) that include a 25 aa signal sequence and a 318 aa mature, secreted protein containing one potential N-linked glycosylation site followed by a Cys-rich domain (aa 268 ‑ 327). The pattern of cysteines is similar to the second of two cysteine-rich regions in members of the DKK family of Wnt inhibitors (4). Mature mouse Draxin (aa 26 ‑ 343) shares 80%, 94%, 77% and 76% aa identity with mature human, mouse, equine and bovine Draxin, respectively. Draxin is a repulsive guidance molecule that, like DKKs, acts as a Wnt antagonist by binding to LRP6 (4). Draxin is expressed by midline glial cells that act as intermediate guideposts for corpus callosum axons (1). Inactivation of the mouse Draxin gene results in lack of organization of axons into functional tracts or bundles (fasciculation), and failure of the corpus callosum, hippocampal and anterior commissures to form and cross the midline (1). Draxin-deficient mice also show abnormally small hippocampi, especially within the dentate gyrus, where excess apoptosis is detected during early postnatal life (3). In vitro, Draxin blocks migration of chick neural crest cells and inhibits neurite outgrowth from dorsal spinal cord explants and dorsal tectum explants of chick embryo. In vivo, ectopic over-expression inhibits growth and disrupts the routing of commissural axons of chick spinal cord and dorsal tectum axons (1, 2, 5).