Netrin-1 is a protein that in humans is encoded by the NTN1 gene.[5][6]
Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon guidance and cell migration during development. Mutations and loss of expression of netrin suggest that variation in netrin may be involved in cancer development.[6]
Interactions
NTN1 has been shown to interact with Deleted in Colorectal Cancer,[5][7] and components of the extracellular matrix and the tumor microenvironment.[8]
Midline Crossing of Commissural Axons
During the development of the central nervous system, when the dorsal and ventral signaling is being established, the floor plate is an important site for crossing for groups of neural processes at the dorsal midline. Once crossed through the floor plate, these groups are now referred to as commissural axons. These neuronal cell bodies are signaled by Netrin 1 to be attracted to the floor plate from the dorsal half of the neural tube. NTN1 is a gene that encodes for the protein, Netrin-1. In a study done in knockout mice with a depletion of floor plate Netrin-1, it was shown that corticospinal axon tract midline crossing was disrupted.[9] This study was done to show characteristics of patients with human congenital mirror movement disorder.
Afterwards, proper positioning of axons and midline crossing are pioneered by the Slit-Robo system where Slit proteins act as axonal repellents and Robo proteins (Robo-1, Robo-2, Robo-3) act in conjunction with Slit ligands to be their receptors.[10] Slit with Robo-1 and Robo-2 repel axonal extension at the midline thereby commissural axons expressing Robo-3 cross the midline by interfering with Slit/Robo-1, Robo-2 repulsive activity. After crossing the floor plate, Robo-3 is downregulated and Slit/Robo-1, Robo-2 continue to express their repulsiveness at the midline. Furthermore, mutations in Robo-3 cause horizontal gaze palsy with progressive scoliosis.
References
Further reading
Varadarajan, Supraja G., et al. "Netrin1 produced by neural progenitors, not floor plate cells, is required for axon guidance in the spinal cord." Neuron 94.4 (2017): 790-799.https://doi.org/10.1016/j.neuron.2017.03.007
External links
- NTN1 human gene location in the UCSC Genome Browser.
- NTN1 human gene details in the UCSC Genome Browser.