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 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.
Wang
H
H
Departments of Anatomy, and Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0452, USA.
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Tessier-Lavigne
M
M
D000818:Animals; D001369:Axons / Q000737:chemistry* / Q000502:physiology; D015152:Blotting, Northern; D002478:Cells, Cultured; D002642:Chick Embryo; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D017950:Ganglia, Sensory / Q000737:chemistry* / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D000075386:Netrin Receptors; D000075388:Netrin-1; D000075385:Netrins; D017933:Peripheral Nervous System / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology; D014162:Transfection; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D000075388:Netrin-1; D000075385:Netrins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C000617351:NTN1 protein, human; C000617353:Ntn1 protein, mouse; C000617308:Unc5A protein, mouse; C091279:neogenin; C119569:netrin-3; C000617307:Unc5b protein, mouse