Developmental cell death in vivo: rescue of neurons independently of changes at target tissues.
Programmed cell death is a prominent feature of neural development that is regulated by a variety of cell-cell interactions. We used the avian ciliary ganglion to dissect the relative contributions of target tissues vs. ganglionic inputs in regulating cell death. The two populations of the ciliary ganglion innervate different targets: choroid neurons innervate vasculature, whereas ciliary neurons innervate the iris and ciliary body. By counting after labeling all neurons with Islet-1 and choroid neurons with anti-somatostatin, we determined that alpha-bungarotoxin (alpha-btx) at 12.5 microg/day rescued only ciliary neurons, whereas 75 microg/day rescued both ciliary and choroid neurons. It is unlikely that alpha-btx acted by blocking nerve transmission at both targets because the choroid vasculature lacked transcripts for alpha-btx binding molecules. In addition, no inherent trophic activity could be ascribed to alpha-btx, and survival could not be attributed to differences in total trophic activity of eyes from saline vs. alpha-btx-treated embryos. In contrast, the alpha7 antagonist alpha-methyllycaconitine (MLA) rescued ciliary neurons at 2.6 microg/day, whereas 26 microg/day rescued choroid neurons. Nerve terminals of ciliary neurons rescued with alpha-btx were significantly larger; however, differences in nerve terminal size or branching of axons were not observed in ciliary neurons rescued with MLA or choroid neurons rescued by either MLA or alpha-btx. Our results suggest that neuronal survival can be promoted independently of changes at the target tissues when orthograde signals acting by means of neuronal alpha7 nicotinic receptors are blocked.
Neuroscience Graduate Program, Oregon Health and Science University, Portland, Oregon 97201, USA.
Gillian L
GL
Bunker
Rae
R
Nishi
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002038:Bungarotoxins / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002829:Choroid / Q000294:innervation*; D002924:Ciliary Body / Q000294:innervation*; D019610:Cytoprotection / Q000502:physiology; D017950:Ganglia, Sensory / Q000502:physiology*; D007498:Iris / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000096:biosynthesis; D011978:Receptors, Nicotinic / Q000096:biosynthesis; D013569:Synapses / Q000187:drug effects
D002038:Bungarotoxins; D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; D018722:Nicotinic Agonists; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; C066297:acetylcholine receptor alpha-subunit (125-148); C054634:methyllycaconitine; D000157:Aconitine