Netrin-3, a Mouse Homolog of Human NTN2L, Is Highly Expressed in Sensory Ganglia and Shows Differential Binding to Netrin Receptors

The netrins comprise a small phylogenetically conserved family of guidance cues important for guiding particular axonal growth cones to their targets. Two netrin genes, netrin-1 and netrin-2, have been described in chicken, but in mouse so far a single netrin gene, an ortholog of chick netrin-1, has...

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Published inThe Journal of neuroscience Vol. 19; no. 12; pp. 4938 - 4947
Main Authors Wang, Hao, Copeland, Neal G, Gilbert, Debra J, Jenkins, Nancy A, Tessier-Lavigne, Marc
Format Journal Article
LanguageEnglish
Published United States Soc Neuroscience 15.06.1999
Society for Neuroscience
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Abstract The netrins comprise a small phylogenetically conserved family of guidance cues important for guiding particular axonal growth cones to their targets. Two netrin genes, netrin-1 and netrin-2, have been described in chicken, but in mouse so far a single netrin gene, an ortholog of chick netrin-1, has been reported. We report the identification of a second mouse netrin gene, which we name netrin-3. Netrin-3 does not appear to be the ortholog of chick netrin-2 but is the ortholog of a recently identified human netrin gene termed NTN2L ("netrin-2-like"), as evidenced by a high degree of sequence conservation and by chromosomal localization. Netrin-3 is expressed in sensory ganglia, mesenchymal cells, and muscles during the time of peripheral nerve development but is largely excluded from the CNS at early stages of its development. The murine netrin-3 protein binds to netrin receptors of the DCC (deleted in colorectal cancer) family [DCC and neogenin] and the UNC5 family (UNC5H1, UNC5H2 and UNC5H3). Unlike chick netrin-1, however, murine netrin-3 binds to DCC with lower affinity than to the other four receptors. Consistent with this finding, although murine netrin-3 can mimic the outgrowth-promoting activity of netrin-1 on commissural axons, it has lower specific activity than netrin-1. Thus, like netrin-1, netrin-3 may also function in axon guidance during development but may function predominantly in the development of the peripheral nervous system and may act primarily through netrin receptors other than DCC.
AbstractList The netrins comprise a small phylogenetically conserved family of guidance cues important for guiding particular axonal growth cones to their targets. Two netrin genes, netrin-1 and netrin-2, have been described in chicken, but in mouse so far a single netrin gene, an ortholog of chick netrin-1, has been reported. We report the identification of a second mouse netrin gene, which we name netrin-3. Netrin-3 does not appear to be the ortholog of chick netrin-2 but is the ortholog of a recently identified human netrin gene termed NTN2L ("netrin-2-like"), as evidenced by a high degree of sequence conservation and by chromosomal localization. Netrin-3 is expressed in sensory ganglia, mesenchymal cells, and muscles during the time of peripheral nerve development but is largely excluded from the CNS at early stages of its development. The murine netrin-3 protein binds to netrin receptors of the DCC (deleted in colorectal cancer) family [DCC and neogenin] and the UNC5 family (UNC5H1, UNC5H2 and UNC5H3). Unlike chick netrin-1, however, murine netrin-3 binds to DCC with lower affinity than to the other four receptors. Consistent with this finding, although murine netrin-3 can mimic the outgrowth-promoting activity of netrin-1 on commissural axons, it has lower specific activity than netrin-1. Thus, like netrin-1, netrin-3 may also function in axon guidance during development but may function predominantly in the development of the peripheral nervous system and may act primarily through netrin receptors other than DCC.
The netrins comprise a small phylogenetically conserved family of guidance cues important for guiding particular axonal growth cones to their targets. Two netrin genes, netrin-1 and netrin-2 , have been described in chicken, but in mouse so far a single netrin gene, an ortholog of chick netrin-1 , has been reported. We report the identification of a second mouse netrin gene, which we name netrin-3 . Netrin-3 does not appear to be the ortholog of chick netrin-2 but is the ortholog of a recently identified human netrin gene termed NTN2L (“netrin-2-like”), as evidenced by a high degree of sequence conservation and by chromosomal localization. Netrin-3 is expressed in sensory ganglia, mesenchymal cells, and muscles during the time of peripheral nerve development but is largely excluded from the CNS at early stages of its development. The murine netrin-3 protein binds to netrin receptors of the DCC (deleted in colorectal cancer) family [DCC and neogenin] and the UNC5 family (UNC5H1, UNC5H2 and UNC5H3). Unlike chick netrin-1, however, murine netrin-3 binds to DCC with lower affinity than to the other four receptors. Consistent with this finding, although murine netrin-3 can mimic the outgrowth-promoting activity of netrin-1 on commissural axons, it has lower specific activity than netrin-1. Thus, like netrin-1, netrin-3 may also function in axon guidance during development but may function predominantly in the development of the peripheral nervous system and may act primarily through netrin receptors other than DCC.
Author Gilbert, Debra J
Jenkins, Nancy A
Tessier-Lavigne, Marc
Copeland, Neal G
Wang, Hao
AuthorAffiliation 1 Departments of Anatomy, and Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0452, and
2 Mammalian Genetics Laboratory, Advanced Bioscience Laboratories Basic Research Program, Frederick Cancer Research and Development Center at the National Cancer Institute, Frederick, Maryland 21702
AuthorAffiliation_xml – name: 2 Mammalian Genetics Laboratory, Advanced Bioscience Laboratories Basic Research Program, Frederick Cancer Research and Development Center at the National Cancer Institute, Frederick, Maryland 21702
– name: 1 Departments of Anatomy, and Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0452, and
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  article-title: Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DNA sequences in chromosomes of Mus musculus.
  publication-title: J Virol
  doi: 10.1128/jvi.43.1.26-36.1982
  contributor:
    fullname: Jenkins
– volume: 10
  start-page: 35
  year: 1999
  ident: 2023041302420549000_19.12.4938.22
  article-title: Netrin-1 interaction with deleted in colorectal cancer (DCC) and alterations in brain tumors and neuroblastomas.
  publication-title: Cell Growth Differ
  contributor:
    fullname: Meyerhardt
– ident: 2023041302420549000_19.12.4938.25
– ident: 2023041302420549000_19.12.4938.7
  doi: 10.1016/S0896-6273(00)80413-4
SSID ssj0007017
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Snippet The netrins comprise a small phylogenetically conserved family of guidance cues important for guiding particular axonal growth cones to their targets. Two...
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StartPage 4938
SubjectTerms Animals
Axons - chemistry
Axons - physiology
Blotting, Northern
Cells, Cultured
Chick Embryo
Chromosome Mapping
Cloning, Molecular
DNA Primers
Female
Ganglia, Sensory - chemistry
Ganglia, Sensory - cytology
Ganglia, Sensory - embryology
Gene Expression Regulation, Developmental
Humans
Male
Membrane Proteins - metabolism
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Motor Neurons - chemistry
Motor Neurons - physiology
Motor Neurons - ultrastructure
Nerve Growth Factors - metabolism
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Netrin Receptors
Netrin-1
Netrins
Peripheral Nervous System - chemistry
Peripheral Nervous System - cytology
Peripheral Nervous System - embryology
Radioligand Assay
Receptors, Cell Surface - metabolism
Recombinant Fusion Proteins - metabolism
RNA, Messenger - analysis
Sequence Homology, Amino Acid
Spinal Cord - chemistry
Spinal Cord - cytology
Transfection
Tumor Suppressor Proteins
Title Netrin-3, a Mouse Homolog of Human NTN2L, Is Highly Expressed in Sensory Ganglia and Shows Differential Binding to Netrin Receptors
URI http://www.jneurosci.org/cgi/content/abstract/19/12/4938
https://www.ncbi.nlm.nih.gov/pubmed/10366627
https://search.proquest.com/docview/17261488
https://search.proquest.com/docview/69825203
https://pubmed.ncbi.nlm.nih.gov/PMC6782680
Volume 19
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