Netrin-1 and DCC Mediate Axon Guidance Locally at the Optic Disc: Loss of Function Leads to Optic Nerve Hypoplasia

نویسندگان

  • Michael S Deiner
  • Timothy E Kennedy
  • Amin Fazeli
  • Tito Serafini
  • Marc Tessier-Lavigne
  • David W Sretavan
چکیده

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.

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عنوان ژورنال:
  • Neuron

دوره 19  شماره 

صفحات  -

تاریخ انتشار 1997