The Netrins (whose name means “one who guides” in Sanskrit) are a family of laminin-related secreted protein. In mice, human and rat, netrin-1, netrin-3/NTL2, Netrin-4 and G-Netrins have been cloned. Netrin-1 is predominantly expressed by floor plate cells as commissural axons extend toward the ventral midline. Netrin-1 induces axonal outgrowth, axon orientation and neuronal migration in neuronal development. It is chemoattractive for some neurons and chemorepellent for others. To carry its functions, netrin-1 interacts with specific receptors: DCC/Neogenin and UNC-5. These receptors belong to the family of “dependence receptors” that induce apoptosis in the absence of their respective ligand, and promote survival when bound to their ligand. The Netrin-1 mediated survival signal inhibits p53-induced apoptosis. Netrin-1 is also expressed in organs such as pancreas, lung, bowel, bone and mammary gland. In these tissues, netrin-1 has different roles such as invasion of epithelial cells, leukocytes migration, cell adhesion or angiogenesis. Netrin-1, as a survival factor, also contributes to the control of tumorigenesis. Historical results have shown that netrin-1 induces axon outgrowth and inhibits DCC- and UNC5H2-mediated apoptosis in HEK 293 cells.
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