NTN1

Netrin-1 (NTN1) is a secreted extracellular guidance cue that plays a central role in axon pathfinding and vascular development. The NTN1 gene encodes the netrin-1 protein, which is highly conserved across vertebrates and operates as a morphogen that can attract or repel navigating cells and growth cones, depending on receptor context.

Expression of netrin-1 occurs in a variety of developing tissues, notably along the central nervous system midline, including the floor plate, where it helps establish directional cues for growing axons. Netrin-1 is also produced by non-neural tissues and can influence cell migration and tissue morphogenesis in multiple organ systems.

Netrin-1 signals primarily through receptors such as DCC (Deleted in Colorectal Cancer) and the UNC5 family. Binding to DCC generally promotes attraction toward the netrin-1 source, whereas the combination of DCC with UNC5 receptors can convert signaling to repulsion. Neogenin can function as an additional netrin receptor in certain contexts. Intracellular signaling downstream of netrin-1 involves pathways that regulate the cytoskeleton and growth cone dynamics, including kinases and small GTPases that control movement and adhesion.

In development, netrin-1 contributes to the proper formation of neural networks by guiding commissural and other axons across the midline and by influencing neuronal positioning. It also participates in vascular patterning and angiogenesis, linking neural and vascular development processes.

Clinical and research significance: Alterations in netrin-1 signaling have been studied in the context of developmental brain connectivity defects in animal models, and netrin-1 pathways are investigated for potential roles in human neurodevelopmental disorders and cancer cell migration. The molecule remains a focus of research on how guidance cues shape tissue organization.