Retinal ganglion cells do not extend axons by default: promotion by neurotrophic signaling and electrical activity.
We investigate the signaling mechanisms that induce retinal ganglion cell (RGC) axon elongation by asking whether surviving neurons extend axons by default. We show that bcl-2 overexpression is sufficient to keep purified RGCs alive in the absence of any glial or trophic support. The bcl-2-expressing RGCs do not extend axons or dendrites unless signaled to do so by single peptide trophic factors. Axon growth stimulated by peptide trophic factors is remarkably slow but is profoundly potentiated by physiological levels of electrical activity spontaneously generated within embryonic explants or mimicked on a multielectrode silicon chip. These findings demonstrate that these surviving neurons do not constitutively extend axons and provide insight into the signals that may be necessary to promote CNS regeneration.
Goldberg
Jeffrey L
JL
Department of Neurobiology, Stanford University School of Medicine, Sherman Fairchild Science Building D231, 299 Campus Drive, Stanford, CA 94305, USA. jlgoldbe@stanford.edu
Espinosa
Juan S
JS
Xu
Youfeng
Y
Davidson
Norman
N
Kovacs
Gregory T A
GT
Barres
Ben A
BA
D000818:Animals; D001369:Axons / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D017077:Culture Media, Conditioned; D004594:Electrophysiology / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014795:Visual Pathways / Q000166:cytology / Q000378:metabolism
D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D006133:Growth Substances; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D005576:Colforsin