PMID- 17286628
OWN - NLM
STAT- MEDLINE
DCOM- 20070501
LR  - 20150813
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 100
IP  - 6
DP  - 2007 Mar
TI  - Truncated tyrosine kinase B brain-derived neurotrophic factor receptor directs 
      cortical neural stem cells to a glial cell fate by a novel signaling mechanism.
PG  - 1515-30
AB  - During development of the mammalian cerebral cortex neural stem cells (NSC) first 
      generate neurons and subsequently produce glial cells. The mechanism(s) 
      responsible for this developmental shift from neurogenesis to gliogenesis is 
      unknown. Brain-derived neurotrophic factor (BDNF) is believed to play important 
      roles in the development of the mammalian cerebral cortex; it enhances 
      neurogenesis and promotes the differentiation and survival of newly generated 
      neurons. Here, we provide evidence that a truncated form of the BDNF receptor 
      tyrosine kinase B (trkB-t) plays a pivotal role in directing embryonic mouse 
      cortical NSC to a glial cell fate. Expression of trkB-t promotes differentiation 
      of NSC toward astrocytes while inhibiting neurogenesis both in cell culture and 
      in vivo. The mechanism by which trkB-t induces astrocyte genesis is not simply 
      the result of inhibition of full-length receptor with intrinsic tyrosine kinase 
      activity signaling. Instead, binding of BDNF to trkB-t activates a signaling 
      pathway (involving a G-protein and protein kinase C) that induced NSC to become 
      glial progenitors and astrocytes. Thus, the increased expression of trkB-t in the 
      embryonic cerebral cortex that occurs coincident with astrocyte production plays 
      a pivotal role in the developmental transition from neurogenesis to gliogenesis. 
      Our findings suggest a mechanism by which a single factor (BDNF) regulates the 
      production of the two major cell types in the mammalian cerebral cortex.
FAU - Cheng, Aiwu
AU  - Cheng A
AD  - Laboratory of Neurosciences, National Institute on Aging Intramural Research 
      Program, Baltimore, Maryland 21224, USA. chengai@grc.nia.nih.gov
FAU - Coksaygan, Turhan
AU  - Coksaygan T
FAU - Tang, Hongyan
AU  - Tang H
FAU - Khatri, Rina
AU  - Khatri R
FAU - Balice-Gordon, Rita J
AU  - Balice-Gordon RJ
FAU - Rao, Mahendra S
AU  - Rao MS
FAU - Mattson, Mark P
AU  - Mattson MP
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20061222
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cell Death/drug effects
MH  - Cell Differentiation/drug effects/physiology
MH  - Cells, Cultured
MH  - Cerebral Cortex/*cytology
MH  - Dose-Response Relationship, Drug
MH  - Embryo, Mammalian
MH  - Enzyme Inhibitors/pharmacology
MH  - Fluorescent Antibody Technique/methods
MH  - Gene Expression Regulation, Enzymologic/drug effects/physiology
MH  - Mice
MH  - Nerve Tissue Proteins/metabolism
MH  - Neuroglia/*physiology
MH  - Neurons/*physiology
MH  - Receptor, trkB/*physiology
MH  - Signal Transduction/drug effects/*physiology
MH  - Stem Cell Transplantation/methods
MH  - Stem Cells/drug effects/*physiology
EDAT- 2007/02/09 09:00
MHDA- 2007/05/02 09:00
CRDT- 2007/02/09 09:00
PHST- 2007/02/09 09:00 [pubmed]
PHST- 2007/05/02 09:00 [medline]
PHST- 2007/02/09 09:00 [entrez]
AID - JNC4337 [pii]
AID - 10.1111/j.1471-4159.2006.04337.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 Mar;100(6):1515-30. doi: 10.1111/j.1471-4159.2006.04337.x. Epub 
      2006 Dec 22.