Complementary expression and neurite outgrowth activity of netrin-G subfamily members (original) (raw)
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The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000
The thalamocortical axon (TCA) projection originates in dorsal thalamus, conveys sensory input to the neocortex, and has a critical role in cortical development. We show that the secreted axon guidance molecule netrin-1 acts in vitro as an attractant and growth promoter for dorsal thalamic axons and is required for the proper development of the TCA projection in vivo. As TCAs approach the hypothalamus, they turn laterally into the ventral telencephalon and extend toward the cortex through a population of netrin-1-expressing cells. DCC and neogenin, receptors implicated in mediating the attractant effects of netrin-1, are expressed in dorsal thalamus, whereas unc5h2 and unc5h3, netrin-1 receptors implicated in repulsion, are not. In vitro, dorsal thalamic axons show biased growth toward a source of netrin-1, which can be abolished by netrin-1-blocking antibodies. Netrin-1 also enhances overall axon outgrowth from explants of dorsal thalamus. The biased growth of dorsal thalamic axons...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000
UNC-6/netrins compose a small phylogenetically conserved family of proteins that act as axon guidance cues. With a signal sequence trap method, we isolated a cDNA encoding a novel member of the UNC-6/netrin family, which we named netrin-G1. Unlike classical netrins, netrin-G1 consists of at least six isoforms of which five were predominantly anchored to the plasma membrane via glycosyl phosphatidyl-inositol linkages. Netrin-G1 transcripts were first detected in midbrain and hindbrain regions by embryonic day 12 and reached highest levels at perinatal stages in various brain regions, including olfactory bulb mitral cells, thalamus, and deep cerebellar nuclei. Its expression was primarily restricted to the CNS. Interestingly, netrin-G1 proteins did not show appreciable affinity to any netrin receptor examined. Unlike netrin-1, a secreted form of netrin-G1 consistently failed to attract circumferentially growing axons from the cerebellar plate. Our findings suggest that netrin-G1 and i...
A role for netrin-1 in the guidance of cortical efferents
Development
An intermediate target for axons leaving the cerebral cortex in embryonic mammals is the ganglionic eminence (GE), the embryonic precursor of the basal ganglia. The cues that direct these axons over the initial portion of their trajectory are not well understood, but could include both short-range and long-range attractants and repellents. In the present study, we provide evidence that corticofugal axons might be guided at least partly by a diffusible factor or factors originating in the lateral GE and the sulcus between the lateral and medial ridges of the GE (ISS), as well as evidence implicating the axonal chemoattractant netrin-1 in mediating these effects. Explants of lateral GE and ISS obtained from E12.5 and E13.5 mouse forebrain have a strong effect on both the outgrowth and orientation of corticofugal axons when cultured at a distance with explants of embryonic cortex in collagen gels. Netrin-1 mRNA is detected in these target tissues by in situ hybridization, and both netr...
Netrin1 is required for neural and glial precursor migrations into the olfactory bulb
Developmental Biology, 2011
a b s t r a c t Netrin1 (NTN1) deficiency in mouse brain causes defects in axon guidance and cell migration during embryonic development. Here we show that NTN1 is required for olfactory bulb (OB) development at late embryogenesis and at early postnatal stages to facilitate the accumulation of proper numbers of granular and glomerular neuron subtypes and oligodendrocytes into the OB. In addition to the analysis of Ntn1−/− mice we made tissue and neurosphere cultures to clarify the role of NTN1 in the anterior forebrain. We propose that a subset of neural progenitors/precursors requires NTN1 to efficiently enter the rostral migratory stream to migrate into the OB. The analysis of postnatal Ntn1−/− OBs revealed a reduction of specific types of interneurons which have been shown to originate from particular subregions of the lateral ventricle walls. Based on Ntn1 expression in ventral parts of the ventricle walls, we observed a decrease in the mainly ventrally derived type II interneurons that express calcium-binding proteins calretinin and calbindin. Instead, no change in the numbers of dorsally derived tyrosine hydroxylase expressing interneurons was detected. In addition to the specific reduction of type II interneurons, our results indicate that NTN1 is required for oligodendroglial migration into the OB. Furthermore, we characterised the Ntn1 expressing subpopulation of neurosphere-forming cells from embryonic and adult brain as multipotent and self-renewing. However, NTN1 is dispensable for the proliferation of neurosphere forming progenitor cells and for their differentiation.
Monoclonal antibodies discriminating netrin-G1 and netrin-G2 neuronal pathways
Journal of Neuroimmunology, 2007
Netrin-G1 and netrin-G2, belonging to a vertebrate-specific subfamily of the netrin family, distribute on axons of distinct neuronal pathways. To add to the array of molecular probes available for labeling unique neuronal circuits, we generated monoclonal antibodies against the netrin-G1 and netrin-G2 proteins. The monoclonal antibody clones 171A18 and 30B15 differentially labeled specific neuronal circuits, the so-called netrin-G1 or netrin-G2 circuits in mice, respectively. Epitope mapping revealed linear epitopes for these monoclonal antibodies, which are common among splicing variants, and suggested that the anti-netrin-G1 monoclonal antibodies are applicable to various species including humans.
Human netrin-G1 isoforms show evidence of differential expression
Genomics, 2005
The recently identified netrins-G1 and -G2 form a distinct subgroup within the UNC-6/netrin gene family of axon guidance molecules. In this study, we determined the size and structure of the exon/intron layout of the human netrin-G1 (NTNG1) and -G2 (NTNG2) genes. Northern analysis of both genes showed limited nonneuronal but wide brain expression, particularly for NTNG2. Reverse transcriptase PCR detected nine alternatively spliced isoforms including four novel variants of NTNG1 from adult brain. A semiquantitative assay established that major expression was restricted to isoforms G1c, G1d, G1a, and G1e in the brain and to G1c in the kidney. There is also evidence of developmental regulation of these isoforms between fetal and adult brain. In conclusion, NTNG1 may use alternative splicing to diversify its function in a developmentally and tissue-specific manner. D
The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6
Cell, 1994
In vertebrates, commissural axons pioneer a clrcumferentlal pathway to the floor plate at the ventral midline of the embryonic spinal cord. Floor plate cells secrete a diffusible factor that promotes the outgrowth of commlssural axons In vitro. We have purified from embryonic chick braln two protelns, netrin-1 and netrln-2, that each possess commissural axon outgrowth-promoting actlvlty, and we have also identlfied a distinct activity that potentiates their effects. Cloning of cDNAsencoding the two netrins shows that they are homologous to UNC-6, a laminln-related protein required for the circumferential migration of cells and axons in C. elegans. This homology suggests that growth cones In the vertebrate spinal cord and the nematode are responsive to similar molecular cues.