Netrin

Netrins are a family of secreted proteins that function as guidance cues during axon development and cell migration. They are primarily known for their role in attracting axons across the midline of the developing nervous system, particularly in the spinal cord. However, they also participate in a wider range of developmental processes, including angiogenesis (blood vessel formation) and the migration of certain cell types during organogenesis.

Netrins exert their effects by binding to transmembrane receptors, primarily of the DCC (Deleted in Colorectal Cancer) family and the UNC-5 (Uncoordinated-5) family. These receptors initiate intracellular signaling cascades that can lead to changes in the cytoskeleton, cell adhesion, and gene expression, ultimately directing the movement of growth cones (the motile tips of axons) or migrating cells.

Netrin-1 is the best-characterized member of the Netrin family. It acts as a chemoattractant for axons expressing the DCC receptor. However, the presence of UNC-5 receptors can modify the response to Netrin-1, causing repulsion instead of attraction. This switch in response is crucial for directing axons to different targets during development.

Different Netrin family members, such as Netrin-3 and Netrin-4, exhibit tissue-specific expression patterns and contribute to distinct developmental processes. Mutations in genes encoding Netrins or their receptors have been implicated in a variety of developmental disorders, highlighting the importance of these proteins in normal development. Research continues to uncover the diverse roles of Netrins in both development and potentially in disease, including cancer.