TrkB/BDNF signaling regulates photoreceptor progenitor cell fate decisions

Abstract

Neurotrophins, via activation of Trk receptor tyrosine kinases, serve as mitogens, survival factors and regulators of arborization during retinal development. Brain-derived neurotrophic factor (BDNF) and TrkB regulate neuronal arborization and survival in late retinal development. However, TrkB is expressed during early retinal development where its functions are unclear. To assess TrkB/BDNF actions in the early chick retina, replication-incompetent retroviruses were utilized to over-express a dominant negative truncated form of TrkB (trunc TrkB), or BDNF and effects were assessed at E15. Clones expressing trunc TrkB were smaller than controls, and proliferation and apoptosis assays suggest that decreased clone size correlated with increased cell death when BDNF/TrkB signaling was impaired. Analysis of clonal composition revealed that trunc TrkB over-expression decreased photoreceptor numbers (41%) and increased cell numbers in the middle third of the inner nuclear layer (INL) (23%). Conversely, BDNF over-expression increased photoreceptor numbers (25%) and decreased INL numbers (17%). Photoreceptors over-expressing trunc TrkB demonstrated no increase in apoptosis nor abnormalities in lamination suggesting that TrkB activation is not required for photoreceptor cell survival or migration. These studies suggest that TrkB signaling regulates commitment to and/or differentiation of photoreceptor cells from retinal progenitor cells, identifying a novel role for TrkB/BDNF in regulating cell fate decisions.

Differential effects of ret and TRKB on axonal branching and survival of parasympathetic neurons

“…To test whether TRKB inhibits axonal branching in vivo, as we previously demonstrated in vitro, we infected embryos with a construct previously shown to act as a dominant negative TRKB in chicken embryos (Turner et al,2006; Supporting Information Fig. 2).…”

Roles for γ‐aminobutyric acid in the development of the paraventricular nucleus of the hypothalamus

“…BDNF is a neurotrophic factor that has characterized roles in neuronal growth, migration, survival, and differentiation (Chiaramello et al,2007; Fukumitsu et al,2006; Gorski et al,2003; Turner et al,2006). BDNF is synthesized in specified locations within the embryonic hypothalamus, including a concentrated group of cells synthesizing BDNF in the PVN (Tapia‐Arancibia et al,2004).…”

Astrocytes from acyclic female rats exhibit lowered capacity for neuronal differentiation

“…BDNF and TrkB expression was detected along the rostral migratory pathway in post-natal day 4 mice and inhibition of BDNF/TrkB signaling resulted in impaired migration of neuroblasts from the subventricular zone in vitro (Chiaramello et al , 2007). In retinal progenitor cells, inhibiting TrkB signaling resulted in increased differentiation of cells in the inner nuclear layer and decreased differentiation of photoreceptor cells (Turner et al , 2006). Astrocyte-conditioned media stimulated TrkB signaling in primary hippocampal neurons leading to increased post-synaptic clustering of GABAA receptors, thus influencing inhibitory synapse formation (Elmariah et al , 2005), and TrkB activation of brain-derived endothelial cells resulted in increased production of angiogenic factors (Li et al , 2006).…”