Embryologic experiments in both vertebrates and invertebrates provide evidence that developing axons are guided to
their targets in the nervous system by the combined actions of attractive and repulsive guidance cues . One family of putative guidance cues for developing axons are the netrins, large (approximately
70-80 kD), soluble proteins that show homology in their amino termini to portions of the extracellular matrix molecule
laminin and that have been implicated in axon guidance through distinct and complementary lines of
evidence in worms, flies, and vertebrates. Netrin-1 is a diffusible protein made by floor plate cells; it can attract spinal
commissural axons and repel trochlear axons in vitro.
NCBI Summary:
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. [provided by RefSeq, Jul 2008]
The axonal guidance factor netrin-1 as a potential modulator of swine follicular function. Basini G et al. This study was aimed to improve knowledge about swine ovarian follicular function, paying attention to angiogenesis, since new vessel growth is a fundamental event in ovarian function. In particular, we investigated a potential involvement of netrin-1, a protein known as a guidance axon factor. Firstly, we studied the expression and immunolocalization of netrin-1 in swine ovarian follicle and its effect on cultured swine granulosa cell viability and steroidogenesis. Furthermore, aortic endothelial cells were employed to verify a possible netrin-1 effect on angiogenesis. Our data demonstrate the expression and the presence of netrin-1 in swine follicular fluid; in addition, it was shown that netrin-1 inhibits granulosa cell viability and estradiol 17beta levels while it stimulates progesterone production. Netrin-1 also inhibits aortic endothelial cell growth in the angiogenesis bioassay. This effect appears to be mediated by inhibiting vascular endothelial growth factor and stimulating nitric oxide. Therefore, we hypothesize that netrin-1 could be important for follicular function in the swine.
The netrins are a family of laminin-related molecules.
Koch M, et al 2000 reported
a novel member of the netrin family, beta-netrin, shares homology
with the beta chain of laminin.
They characterize a new
member of the family, beta-netrin. beta-Netrin is homologous to the NH(2) terminus of
laminin chain short arms; it contains a laminin-like domain VI and 3.5 laminin EGF
repeats and a netrin C domain. Unlike other netrins, this netrin is more related to
the laminin beta chains, thus, its name beta-netrin. An initial analysis of the tissue
distribution revealed that kidney, heart, ovary, retina, and the olfactory bulb were
tissues of high expression. beta-Netrin is a basement membrane
component; it is present in the basement membranes of the vasculature, kidney, and
ovaries.
Follicle stages
Antral, Preovulatory
Comment
Netrin-1: Just an axon-guidance factor? Baioni L et al. Netrin-1 was first identified as a guidance factor in axon outgrowth during central nervous system development and was later shown to be involved in the morphogenesis of other organs. This study, thus, aimed to verify netrin-1 gene expression in swine antral follicles and to detect netrin-1 protein expression in follicular fluid. In addition, since netrin-1 is also a potential guidance factor for endothelial cells during angiogenesis, an essential event for follicular development, we attempted to verify its effects on swine aortic endothelial cells. Our results show that netrin-1 is present in follicular fluid and is physiologically expressed in both the thecal and granulosa layers from swine antral follicles. Furthermore, by means of an angiogenesis bioassay, we documented the inhibition of vascular neoformation by netrin-1. In conclusion, our results demonstrate that netrin-1 can be synthesized by swine follicular cells and secreted in the follicular fluid where it appears to exert regulatory effects on both follicular function and vascular development.
Phenotypes
Mutations
3 mutations
Species: D. melanogaster
Mutation name: None
type: null mutation fertility: infertile - ovarian defect Comment: Control of male and female fertility by the netrin axon guidance genes. Newquist G 2013 et al.
The netrin axon guidance genes have previously been implicated in fertility in C. elegans and in vertebrates. Here we show that adult Drosophila lacking both netrin genes, NetA and NetB, have fertility defects in both sexes together with an inability to fly and reduced viability. NetAB females produce fertilized eggs at a much lower rate than wild type. Oocyte development and ovarian innervation are unaffected in NetAB females, and the reproductive tract appears normal. A small gene, hog, that resides in an intron of NetB does not contribute to the NetAB phenotype. Restoring endogenous NetB expression rescues egg-laying, but additional genetic manipulations, such as restoration of netrin midline expression and inhibition of cell death have no effect on fertility. NetAB males induce reduced egg-laying in wild type females and display mirror movements of their wings during courtship. Measurement of courtship parameters revealed no difference compared to wild type males. Transgenic manipulations failed to rescue male fertility and mirror movements. Additional genetic manipulations, such as removal of the enabled gene, a known suppressor of the NetAB embryonic CNS phenotype, did not improve the behavioral defects. The ability to fly was rescued by inhibition of neuronal cell death and pan-neural NetA expression. Based on our results we hypothesize that the adult fertility defects of NetAB mutants are due to ovulation defects in females and a failure to properly transfer sperm proteins in males, and are likely to involve multiple neural circuits.
/////////////////////////
Species: C. elegans
Mutation name: type: null mutation fertility: fertile Comment: UNC-6/netrin and its receptor UNC-5 locally exclude presynaptic components from dendrites. Poon VY et al. (2008) Polarity is an essential feature of many cell types, including neurons that receive information from local inputs within their dendrites and propagate nerve impulses to distant targets through a single axon. It is generally believed that intrinsic structural differences between axons and dendrites dictate the polarized localization of axonal and dendritic proteins. However, whether extracellular cues also instruct this process in vivo has not been explored. Here we show that the axon guidance cue UNC-6/netrin and its receptor UNC-5 act throughout development to exclude synaptic vesicle and active zone proteins from the dendrite of the Caenorhabditis elegans motor neuron DA9, which is proximal to a source of UNC-6/netrin. In unc-6/netrin and unc-5 loss-of-function mutants, presynaptic components mislocalize to the DA9 dendrite. In addition, ectopically expressed UNC-6/netrin, acting through UNC-5, is sufficient to exclude endogenous synapses from adjacent subcellular domains within the DA9 axon. Furthermore, this anti-synaptogenic activity is interchangeable with that of LIN-44/Wnt despite being transduced through different receptors, suggesting that extracellular cues such as netrin and Wnts not only guide axon navigation but also regulate the polarized accumulation of presynaptic components through local exclusion.//////////////////