Disease relevance of Ntn1

• The axonal chemoattractant netrin-1 guides spinal commissural axons by activating its receptor DCC (Deleted in Colorectal Cancer) [1].

High impact information on Ntn1

• Floor plate cells at the ventral midline of the neural tube express a diffusible chemoattractant, netrin-1, that attracts a group of ventrally directed axons [2].
• COS cells secreting recombinant netrin-1 mimic this effect, suggesting that netrin-1 is a bifunctional guidance cue that simultaneously attracts some axons to the floor plate while steering others away [2].
• These results show that netrin-1 is a chemotropic factor expressed by floor plate cells and suggest that the two netrin proteins guide commissural axons in the developing spinal cord [3].
• Ectopic expression of DCC produced a netrin-1-dependent increase in the number of filopodia and in cell surface area [4].
• To determine whether netrin receptors (DCC, UNC5H1, UNC5H2) and netrin-1 are present in the adult rat retina and may affect regeneration of retinal ganglion cell (RGC) axons into peripheral nerve (PN) grafts, in situ hybridization (ISH) and immunostaining experiments were performed in normal and operated rats [5].

Biological context of Ntn1

• While unilateral bulbectomy induced a transient up-regulation of netrin-1 in the lamina propria, particularly in the dorso-medial region of the neuroepithelium, no DCC expression was detected on the regenerating olfactory axons [6].
• These findings suggest that unc-5 homologues constitute a major mode of netrin-1 signal transduction in the adult spinal cord and may be involved in phenomena analogous to axon repulsion, such as inhibiting process extension and collateral sprouting [7].
• The deduced proteins of the variants had truncated C-termini, however, the two key functional protein domains, the cysteine-rich domain and the netrin-like domain of the isoforms, were not altered [8].
• A late effect of the neonatal testosterone propionate treatment on netrin-1, growth-associated protein, olfactory marker protein, collapsin response mediator proteins 1, 3, 4 and cypin gene expression was observed [9].
• The protein product of the deleted in colorectal cancer (DCC) gene possesses netrin-binding activity and may be involved in axonal guidance during retinal development [10].

Anatomical context of Ntn1

• We show here that netrin-1 RNA is expressed by floor plate cells, whereas netrin-2 RNA is detected at lower levels in the ventral two-thirds of the spinal cord, but not the floor plate [3].
• Netrin-1, a diffusible signal secreted by floor plate cells at the ventral midline of the vertebrate CNS, can attract ventrally migrating axons and repel a subset of dorsally migrating axons in the spinal cord and rostral hindbrain in vitro [11].
• Netrin-1 expression was not found in the optic nerve head of adult rats, normal and postlesion, but appeared transiently at 7 and 14 days after PN grafting [5].
• We show that the netrin-1 receptor, deleted in colorectal cancer (DCC), is present at filopodia tips in growth cones of embryonic rat spinal commissural neurons [4].
• Explants from the ventral region of the caudal diencephalon where netrin-1 is expressed attracted the axons from habenular explants [12].

Associations of Ntn1 with chemical compounds

• Our data demonstrated that glucose-induced aging in vitro caused an elongation and thickening of cell processes and significantly increased the expression of netrin reflecting a more mature state of oligodendrocyte development [13].

Other interactions of Ntn1

• Here we show that the netrin receptors dcc, neogenin, unc5h1, unc5h2, and unc5h3 are also expressed in the adult rat spinal cord [7].
• These results suggest that the growth of axons from the habenular nucleus along the neuromere boundary region may be regulated by Sema3F from the rostral p1, and netrin-1 from the ventral region of the caudal diencephalon [12].
• In this study, we examined the spatio-temporal expression patterns of both netrin-1 and DCC in the rat olfactory system at different stages of development and during axonal regeneration following unilateral bulbectomy [6].

Analytical, diagnostic and therapeutic context of Ntn1

• Multiple mRNA transcripts detected by Northern blot analysis suggested that netrin receptors might be encoded by alternatively spliced mRNAs [7].
• The PCR data show that netrin-1 mRNA is normally expressed at low levels in peripheral nerve, and similar low levels are found 2 weeks following a crush injury [14].
• The present study utilized competitive PCR and immunohistochemistry to demonstrate the localization of netrin-1 within adult rat sciatic nerve [14].
• Expression of netrin-1 and its receptors DCC and UNC-5H2 after axotomy and during regeneration of adult rat retinal ganglion cells [15].
• Northern blot analysis demonstrated expression of netrin-1 in both optic and sciatic nerve, and Western blot analysis revealed the presence of netrin protein in both nerves [15].

References