Netrin-G1: a Novel Glycosyl Phosphatidylinositol-Linked Mammalian Netrin That Is Functionally Divergent from Classical Netrins

Ikeda, Toshio; Nishimura, Shigehiro; Tashiro, Kei; Honjo, Tasuku; Culotti, Joseph G.; Itohara, Shigeyoshi

doi:10.1523/jneurosci.20-17-06540.2000

Cited by 146 publications

(138 citation statements)

References 52 publications

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“…2B). Several of these mRNAs are known to be have roles in brain function, including Ntng1 (Nakashiba et al 2000), Dlgh2/ PSD93 (Tao et al 2003;Parker et al 2004), Nell2 (Matsuyama et al 2004), and Gabrg2 (Gunther et al 1995). Clearly, it will be interesting to follow up in future studies whether the ncRNAs identified here play any role in the biology of the mRNAs whose expression patterns they share.…”

Section: Tissue Profiling Of Putative Ncrnasmentioning

confidence: 85%

Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome

Ravasi¹,

Suzuki²,

Pang³

et al. 2005

Genome Res.

473

364

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Recent large-scale analyses of mainly full-length cDNA libraries generated from a variety of mouse tissues indicated that almost half of all representative cloned sequences did not contain an apparent protein-coding sequence, and were putatively derived from non-protein-coding RNA (ncRNA) genes. However, many of these clones were singletons and the majority were unspliced, raising the possibility that they may be derived from genomic DNA or unprocessed pre-mRNA contamination during library construction, or alternatively represent nonspecific "transcriptional noise." Here we show, using reverse transcriptase-dependent PCR, microarray, and Northern blot analyses, that many of these clones were derived from genuine transcripts of unknown function whose expression appears to be regulated. The ncRNA transcripts have larger exons and fewer introns than protein-coding transcripts. Analysis of the genomic landscape around these sequences indicates that some cDNA clones were produced not from terminal poly(A) tracts but internal priming sites within longer transcripts, only a minority of which is encompassed by known genes. A significant proportion of these transcripts exhibit tissue-specific expression patterns, as well as dynamic changes in their expression in macrophages following lipopolysaccharide stimulation. Taken together, the data provide strong support for the conclusion that ncRNAs are an important, regulated component of the mammalian transcriptome.[Supplemental material is available online at www.genome.org. The microarray data from this study have been submitted to the Gene Expression Omnibus under accession nos. GSD275 and GSE3098.] In recent years there have been increasing reports of functional non-protein-coding RNAs (ncRNAs) that are involved or implicated in developmental, tissue-specific, and disease processes, including X-chromosome dosage compensation, germ cell development and embryogenesis, neural and immune cell development, kidney and testis development, B-cell neoplasia, lung cancer, prostate cancer, cartilage-hair hypoplasia, spinocerebellar ataxia type 8, DiGeorge syndrome, autism, and schizophrenia (see Pang et al. 2005). Many putative ncRNAs are alternatively spliced and/or polyadenylated (Sutherland et al. 1996;Tam et al. 1997;Bussemakers et al. 1999;Raho et al. 2000;Charlier et al. 2001;Wolf et al. 2001). Smaller ncRNAs, termed microRNAs, have also been shown to be involved in developmental processes in both plants and animals, as well as implicated in disease (Carrington and Ambros 2003;Mattick and Makunin 2005). Recent evidence suggests that these microRNAs are derived from the introns of capped and polyadenylated protein-coding transcripts as well as the exons and introns of non-protein-coding transcripts, many of which are derived from "intergenic" regions (Cai et al. 2004;Rodriguez et al. 2004;Seitz et al. 2004;Mattick and Makunin 2005;Ying and Lin 2005). In addition, many complex genetic phenomena, including cosuppression, imprinting, methylation, and gene silencing (see Mattick...

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Section: Tissue Profiling Of Putative Ncrnasmentioning

confidence: 85%

Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome

Ravasi¹,

Suzuki²,

Pang³

et al. 2005

Genome Res.

473

364

View full text Add to dashboard Cite

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“…Furthermore, Ntng1 proteins lack any appreciable affinity to receptors for classical netrins. 10 Ntng1 transcripts are most abundant in the CNS with highest expression in the dorsal thalamus, olfactory bulb, and inferior colliculus. Interestingly, Ntng1 is also expressed in the cerebellar inferior olive nuclei, and Figure 4 Expression analysis of NTNG1 in the patient.…”

Section: Discussionmentioning

confidence: 99%

Disruption of Netrin G1 by a balanced chromosome translocation in a girl with Rett syndrome

et al. 2005

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We have identified a girl with characteristic features of Rett syndrome (RTT) who carries a de novo balanced translocation involving chromosomes 1 and 7. Both breakpoints were mapped by fluorescence in situ hybridization with selected genomic clones from the regions of interest. Southern blot hybridisations, utilizing probes derived from breakpoint spanning BACs, detected several aberrant fragments specific for the patient. Sequence analysis of the cloned junction fragment indicated that on chromosome 1 the predominantly brain-expressed Netrin G1 (NTNG1) gene is disrupted, whereas on chromosome 7 there was no indication for a truncated gene. The chromosome 1 breakpoint lies within the 3 0 part of NTNG1 and affects alternatively spliced transcripts, suggesting that the phenotype in this patient is the result of disturbed NTNG1 expression. In silico translation of the NTNG1 splice variants predicted protein isoforms with different C-termini: one membrane bound through a glycosylphosphatidylinositol anchor and the other soluble. The membrane-bound protein isoform would be affected by the breakpoint, whereas the soluble form would remain intact. Our results suggest that the central nervous system is sensitive to NTNG1 expression levels and that NTNG1 is a novel candidate disease gene for RTT.

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“…Despite the lack of a mouse ortholog of chick Netrin-2, cDNA clones encoding three additional mouse Netrins have recently been isolated (Puschel, 1999;Nakashiba et al, 2000;Yin et al, 2000). While Netrin-3 (Puschel, 1999; and Netrin-G1, a novel glycosyl phosphatidylinositol (GPI)-linked Netrin (Nakashiba et al, 2000) are not expressed at the ventral midline of the developing spinal cord, mouse Netrin-4 is selectively expressed at the lateral margins of the floor plate (Yin et al, 2000). Thus, Netrin-4 is well-positioned to potentially function as a long-range chemoattractant for a subpopulation of commissural axons in the netrin-1 knockout mice.…”

Section: Long-range Guidance To the Midline Vertebrate Spinal Cord: Nmentioning

confidence: 99%

Axon guidance at the midline choice point

Kaprielian

Runko

Imondi

2001

Developmental Dynamics

146

108

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The central nervous system (CNS) of higher organisms is bilaterally-symmetric. The transfer of information between the two sides of the nervous system occurs through commissures formed by neurons that project axons across the midline to the contralateral side of the CNS. Interestingly, these axons cross the midline only once. Other neurons extend axons that never cross the midline; they project exclusively on their own (ipsilateral) side of the CNS. Thus, the midline is an important choice point for several classes of pathfinding axons. Recent studies demonstrate that specialized midline cells play critical roles in regulating the guidance of both crossing and non-crossing axons at the ventral midline of the developing vertebrate spinal cord and the Drosophila ventral nerve cord. For example, these cells secrete attractive cues that guide commissural axons over long distances to the midline of the CNS. Furthermore, shortrange interactions between guidance cues present on the surfaces of midline cells, and their receptors expressed on the surfaces of pathfinding axons, allow commissural axons to cross the midline only once and prevent ipsilaterally-projecting axons from entering the midline. Remarkably, the molecular composition of commissural axon surfaces is dynamically-altered as they cross the midline. Consequently, commissural axons become responsive to repulsive midline guidance cues that they had previously ignored on the ipsilateral side of the midline. Concomitantly, commissural axons lose responsiveness to attractive guidance cues that had initially attracted them to the midline. Thus, these exquisitely regulated guidance systems prevent commissural axons from lingering within the confines of the midline and allow them to pioneer an appropriate pathway on the contralateral side of the CNS. Many aspects of midline guidance are controlled by mechanistically and evolutionarily-conserved ligand-receptor systems. Strikingly, recent studies demonstrate that these receptors are modular; the ectodomains determine ligand recognition and the cytoplasmic domains specify the response of an axon to a given guidance cue. Despite rapid and dramatic progress in elucidating the molecular mechanisms that control midline guidance, many questions remain.

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Netrin-G1: a Novel Glycosyl Phosphatidylinositol-Linked Mammalian Netrin That Is Functionally Divergent from Classical Netrins

Cited by 146 publications

References 52 publications

Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome

Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome

Disruption of Netrin G1 by a balanced chromosome translocation in a girl with Rett syndrome

Axon guidance at the midline choice point

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