Semaphorin 3E/collapsin-5 inhibits growing retinal axons.
During development, the formation of neural networks is reflected by the oriented extension of neurites. Using retinal ganglion cells (RGCs) as a model, we identified the yet uncharacterized chick semaphorin Sema3E/collapsin-5 as a repulsive cue for outgrowing axons. Sema3E/collapsin-5 was highly regulated during retinal histogenesis, with peak expression during the period of intraretinal axon growth. Polymerase chain reaction analysis demonstrated Sema3E/collapsin-5 mRNA in retina layers, from which RGC axons are excluded. Neither isolated RGCs nor purified retinal Müller glia cells synthesized Sema3E/collapsin-5. Sema3E/collapsin-5 receptor sites were visualized by alkaline phosphatase fusion proteins in the axon-rich optic fiber layer. Time-lapse video recording of chick in vitro cultures revealed a growth cone collapsing activity of recombinant Sema3E/collapsin-5. This effect was specific for RGCs, since dorsal root ganglia (DRG) neurons of the peripheral nervous system were not affected. Comparison with Sema3A/collapsin-1 displayed a reciprocal specificity, because Sema3A/collapsin-1 hampered exclusively DRG but not RGC growth cones. The collapsing effect was mediated by low cGMP levels, but not cAMP, as revealed by a set of agonists. In summary, the data suggest a possible role of chick Sema3E/collapsin-5 in restricting growth of retinal ganglion cell axons to the optic fiber layer.
Steinbach
Karin
K
NMI Naturwissenschaftliches und Medizinisches Institut, Universität Tübingen, Markwiesenstrasse 55, D-72770, Reutlingen, Germany.
Volkmer
Hansjürgen
H
Schlosshauer
Burkhard
B
D000818:Animals; D030161:Avian Proteins; D001369:Axons / Q000648:ultrastructure*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division; D002478:Cells, Cultured; D002642:Chick Embryo; D006152:Cyclic GMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D020439:Growth Cones / Q000648:ultrastructure; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D012160:Retina / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism; D039961:Semaphorins; D015398:Signal Transduction; D014018:Tissue Distribution
D030161:Avian Proteins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C108640:Semaphorin 3E, chicken; D039961:Semaphorins; D006152:Cyclic GMP