Turning of retinal growth cones in a netrin-1 gradient mediated by the netrin receptor DCC.
Netrin-1 promotes outgrowth of axons in vitro through the receptor Deleted in Colorectal Cancer (DCC) and elicits turning of axons within embryonic explants when presented as a point source. It is not known whether netrin-1 alone can elicit turning nor whether DCC mediates the turning response. We show that Xenopus retinal ganglion cell growth cones orient rapidly toward a pipette ejecting netrin-1, an effect blocked by antibodies to DCC. In vitro, netrin-1 induces a complex growth cone morphology reminiscent of that at the optic nerve head, a site of netrin-1 expression in vivo. These results demonstrate that netrin-1 can function alone to induce turning, implicate DCC in this response, and support the idea that netrin-1 contributes to steering axons out of the retina.
de la Torre
J R
JR
Howard Hughes Medical Institute, Department of Anatomy, University of California, San Francisco 94143-0452, USA.
Höpker
V H
VH
Ming
G L
GL
Poo
M M
MM
Tessier-Lavigne
M
M
Hemmati-Brivanlou
A
A
Holt
C E
CE
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D016764:Cell Polarity; D000075389:DCC Receptor; D004625:Embryo, Nonmammalian / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology*; D000075386:Netrin Receptors; D000075388:Netrin-1; D016501:Neurites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009900:Optic Nerve / Q000196:embryology; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000276:immunology / Q000502:physiology*; D012160:Retina / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins; D014981:Xenopus
D000906:Antibodies; D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1