TrkB/BDNF signaling regulates photoreceptor progenitor cell fate decisions.
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.
Turner
Brian A
BA
Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Room C606, New York, NY 10021, USA.
Sparrow
Janet
J
Cai
Bolin
B
Monroe
Julie
J
Mikawa
Takashi
T
Hempstead
Barbara L
BL
D000818:Animals; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002642:Chick Embryo; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology* / Q000502:physiology; D020033:Protein Isoforms / Q000502:physiology; D020813:Receptor, trkB / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D020033:Protein Isoforms; D020813:Receptor, trkB