Target-dependent regulation of retinal nicotinic acetylcholine receptor and tubulin RNAs during optic nerve regeneration in goldfish.
A fundamental issue in central nervous system development regards the effect of target tissue on the differentiation of innervating neurons. We address this issue by characterizing the role the retinal ganglion cell target, i.e., the optic tectum, plays in regulating expression of tubulin and nicotinic acetylcholine receptor genes in regenerating retinal ganglion cells. Tubulins are involved in axonal growth, whereas nicotinic acetylcholine receptors mediate communication across synapses. Retinal ganglion cell axons were induced to regenerate by crushing the optic nerve. Following crush, there was a rapid increase in alpha-tubulin RNAs (3 days), which preceded the increase in nicotinic acetylcholine receptor RNAs (10-15 days). Both classes of RNAs approached control levels by the time retinotectal synapses and functional recovery were restored (4-6 weeks). If the optic nerve was repeatedly crushed or its target ablated, tubulin RNAs remained elevated, and the increase in receptor RNAs that would otherwise be seen 2 weeks after a single nerve crush did not occur. The interaction of retinal ganglion cell axons with their targets in the optic tectum appears, then, to exert a suppressive effect on the RNA encoding a cytoskeletal protein, tubulin, and an inductive effect on RNAs encoding nicotinic acetylcholine receptors involved in synaptic communication.
Mental Health Research Institute, University of Michigan, Ann Arbor 48109.
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V
Hieber
B W
BW
Agranoff
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D
Goldman
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology; D015870:Gene Expression; D006054:Goldfish; D008969:Molecular Sequence Data; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology*; D012313:RNA / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000502:physiology; D013477:Superior Colliculi / Q000502:physiology; D014404:Tubulin / Q000235:genetics*
D011978:Receptors, Nicotinic; D014404:Tubulin; D012313:RNA