Netrin-1 and DCC mediate axon guidance locally at the optic disc: loss of function leads to optic nerve hypoplasia.
Embryonic retinal ganglion cell (RGC) axons must extend toward and grow through the optic disc to exit the eye into the optic nerve. In the embryonic mouse eye, we found that immunoreactivity for the axon guidance molecule netrin-1 was specifically on neuroepithelial cells at the disk surrounding exiting RGC axons, and RGC axons express the netrin receptor, DCC (deleted in colorectal cancer). In vitro, anti-DCC antibodies reduced RGC neurite outgrowth responses to netrin-1. In netrin-1- and DCC-deficient embryos, RGC axon pathfinding to the disc was unaffected; however, axons failed to exit into the optic nerve, resulting in optic nerve hypoplasia. Thus, netrin-1 through DCC appears to guide RGC axons locally at the optic disc rather than at long range, apparently reflecting the localization of netrin-1 protein to the vicinity of netrin-1-producing cells at the optic disc.
Deiner
M S
MS
Department of Ophthalmology, University of California, San Francisco 94143, USA.
Kennedy
T E
TE
Fazeli
A
A
Serafini
T
T
Tessier-Lavigne
M
M
Sretavan
D W
DW
D000818:Animals; D000911:Antibodies, Monoclonal; D001369:Axons / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D001667:Binding, Competitive / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D000075389:DCC Receptor; D004305:Dose-Response Relationship, Drug; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000502:physiology; D009414:Nerve Growth Factors / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D000075388:Netrin-1; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009900:Optic Nerve / Q000002:abnormalities* / Q000196:embryology* / Q000473:pathology; D010857:Pigment Epithelium of Eye / Q000196:embryology / Q000473:pathology; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D000075389:DCC Receptor; C501910:Dcc protein, mouse; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1