PMID- 17005175 OWN - NLM STAT- MEDLINE DCOM- 20070116 LR - 20190508 IS - 0012-1606 (Print) IS - 1095-564X (Electronic) IS - 0012-1606 (Linking) VI - 299 IP - 2 DP - 2006 Nov 15 TI - TrkB/BDNF signaling regulates photoreceptor progenitor cell fate decisions. PG - 455-65 AB - 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. FAU - Turner, Brian A AU - Turner BA AD - Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Room C606, New York, NY 10021, USA. FAU - Sparrow, Janet AU - Sparrow J FAU - Cai, Bolin AU - Cai B FAU - Monroe, Julie AU - Monroe J FAU - Mikawa, Takashi AU - Mikawa T FAU - Hempstead, Barbara L AU - Hempstead BL LA - eng GR - R01 NS030687-14/NS/NINDS NIH HHS/United States GR - R01 EY012951/EY/NEI NIH HHS/United States GR - NS30687/NS/NINDS NIH HHS/United States GR - EY12293/EY/NEI NIH HHS/United States GR - R01 EY012293-03/EY/NEI NIH HHS/United States GR - R01 EY012293-02/EY/NEI NIH HHS/United States GR - R01 NS030687/NS/NINDS NIH HHS/United States GR - R01 EY012293-01A1/EY/NEI NIH HHS/United States GR - R01 EY012951-11/EY/NEI NIH HHS/United States GR - R01 NS030687-13/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060814 PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Protein Isoforms) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Apoptosis MH - Brain-Derived Neurotrophic Factor/genetics/*physiology MH - Cell Differentiation MH - Cell Movement MH - Cell Proliferation MH - Cell Survival MH - Chick Embryo MH - Photoreceptor Cells, Vertebrate/*cytology/physiology MH - Protein Isoforms/physiology MH - Receptor, trkB/genetics/*physiology MH - Retina/*cytology/embryology/metabolism MH - Signal Transduction/*physiology MH - Stem Cells/*cytology/physiology PMC - PMC2623246 MID - NIHMS13716 EDAT- 2006/09/29 09:00 MHDA- 2007/01/17 09:00 PMCR- 2009/01/13 CRDT- 2006/09/29 09:00 PHST- 2005/08/05 00:00 [received] PHST- 2006/08/07 00:00 [revised] PHST- 2006/08/09 00:00 [accepted] PHST- 2006/09/29 09:00 [pubmed] PHST- 2007/01/17 09:00 [medline] PHST- 2006/09/29 09:00 [entrez] PHST- 2009/01/13 00:00 [pmc-release] AID - S0012-1606(06)01093-1 [pii] AID - 10.1016/j.ydbio.2006.08.025 [doi] PST - ppublish SO - Dev Biol. 2006 Nov 15;299(2):455-65. doi: 10.1016/j.ydbio.2006.08.025. Epub 2006 Aug 14.