TrkB receptor signaling regulates developmental death dynamics, but not final number, of retinal ganglion cells
Pollock, G.S.; Robichon, R.; Boyd, K.A.; Kerkel, K.A.; Kramer, M.; Lyles, J.; Ambalavanar, R.; Khan, A.; Kaplan, D.R.; Williams, R.W.; Frost, D.O.
Journal of Neuroscience the Official Journal of the Society for Neuroscience 23(31): 10137-10145
ISSN/ISBN: 0270-6474 PMID: 14602830 Accession: 011596628
We investigated the effects of endogenous neurotrophin signaling on the death-survival of immature retinal ganglion cells (RGCs) in vivo. Null mutation of brain-derived neurotrophic factor ((BDNF) alone or in combination with neurotrophin 4 (NT4)) increases the peak rate of developmental RGC death as compared with normal. Null mutation of NT4 alone is ineffective. Null mutation of the full-length trkB (trkBFL) receptor catalytic domain produces a dose-dependent increase in the peak RGC death rate that is negatively correlated with retinal levels of trkBFL protein and phosphorylated (activated) trkBFL. Depletion of target-derived trkB ligands by injection of trkB-Fc fusion protein into the superior colliculus increases the peak rate of RGC death compared with trkA-Fc-treated and normal animals. Adult trkBFL+/- mice have a normal number of RGCs, despite an elevated peak death rate of immature RGCs. Thus, target-derived BDNF modulates the dynamics of developmental RGC death through trkBFL activation, but BDNF/trkB-independent mechanisms determine the final number of RGCs.