netrin1

Netrin-1 is a secreted laminin-related guidance cue important for axon pathfinding and cell migration during development. It is encoded by the NTN1 gene in vertebrates. The protein belongs to the netrin family and features an N-terminal domain and several laminin-type EGF repeats; it is secreted into the extracellular space and can form gradients that guide migrating cells and growing axons.

Netrin-1 exerts its effects through receptors including DCC (Deleted in Colorectal Cancer) and UNC5 family members. Binding to DCC generally promotes attraction toward the netrin-1 source, whereas interaction with UNC5 receptors mediates chemorepulsion. Neogenin can function as a co-receptor with DCC or UNC5 to modulate responses. The midline of the nervous system, particularly the floor plate in developing spinal cord, is a major source of netrin-1, helping commissural axons approach and cross the midline before changing their responsiveness.

In addition to axon guidance, netrin-1 influences neuronal migration and tissue patterning in the developing brain and other organs, and participates in vascular development, where it can regulate angiogenesis and endothelial cell behavior.

Disruption of netrin-1 signaling, through NTN1 or receptor mutations, affects commissural connectivity and has been linked to congenital brain malformations in model organisms and sometimes humans. In cancer biology, netrin-1 can act as a survival cue for tumor cells via DCC/UNC5 pathways, contributing to tumor progression in some contexts.

Netrin-1 is conserved across species, with genetic and functional homologs identified in invertebrates, illustrating its fundamental role in guiding cellular organization.