PMID- 17254333
OWN - NLM
STAT- MEDLINE
DCOM- 20081201
LR  - 20240413
IS  - 1749-8104 (Electronic)
IS  - 1749-8104 (Linking)
VI  - 2
DP  - 2007 Jan 25
TI  - Neurotrophin/Trk receptor signaling mediates C/EBPalpha, -beta and NeuroD 
      recruitment to immediate-early gene promoters in neuronal cells and requires 
      C/EBPs to induce immediate-early gene transcription.
PG  - 4
AB  - BACKGROUND: Extracellular signaling through receptors for neurotrophins mediates 
      diverse neuronal functions, including survival, migration and differentiation in 
      the central nervous system, but the transcriptional targets and regulators that 
      mediate these diverse neurotrophin functions are not well understood. RESULTS: We 
      have identified the immediate-early (IE) genes Fos, Egr1 and Egr2 as 
      transcriptional targets of brain derived neurotrophic factor (BDNF)/TrkB 
      signaling in primary cortical neurons, and show that the Fos serum response 
      element area responds to BDNF/TrkB in a manner dependent on a combined C/EBP-Ebox 
      element. The Egr1 and Egr2 promoters contain homologous regulatory elements. We 
      found that C/EBPalpha/beta and NeuroD formed complexes in vitro and in vivo, and 
      were recruited to all three homologous promoter regions. C/EBPalpha and NeuroD 
      co-operatively activated the Fos promoter in transfection assays. Genetic 
      depletion of Trk receptors led to impaired recruitment of C/EBPs and NeuroD in 
      vivo, and elimination of Cebpa and Cebpb alleles reduced BDNF induction of Fos, 
      Egr1 and Egr2 in primary neurons. Finally, defective differentiation of cortical 
      dendrites, as measured by MAP2 staining, was observed in both compound Cebp and 
      Ntrk knockout mice. CONCLUSION: We here identify three IE genes as targets for 
      BDNF/TrkB signaling, show that C/EBPalpha and -beta are recruited along with 
      NeuroD to target promoters, and that C/EBPs are essential mediators of Trk 
      signaling in cortical neurons. We show also that C/EBPs and Trks are required for 
      cortical dendrite differentiation, consistent with Trks regulating dendritic 
      differentiation via a C/EBP-dependent mechanism. Finally, this study indicates 
      that BDNF induction of IE genes important for neuronal function depends on 
      transcription factors (C/EBP, NeuroD) up-regulated during neuronal development, 
      thereby coupling the functional competence of the neuronal cells to their 
      differentiation.
FAU - Calella, Anna Maria
AU  - Calella AM
AD  - European Molecular Biology Laboratory, Mouse Biology Unit, via Ramarini, 00016 
      Monterotondo, Italy. AnnaMaria.Calella@usz.ch
FAU - Nerlov, Claus
AU  - Nerlov C
FAU - Lopez, Rodolphe G
AU  - Lopez RG
FAU - Sciarretta, Carla
AU  - Sciarretta C
FAU - von Bohlen und Halbach, Oliver
AU  - von Bohlen und Halbach O
FAU - Bereshchenko, Oksana
AU  - Bereshchenko O
FAU - Minichiello, Liliana
AU  - Minichiello L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070125
PL  - England
TA  - Neural Dev
JT  - Neural development
JID - 101286574
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CCAAT-Enhancer-Binding Protein-alpha)
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (Egr1 protein, mouse)
RN  - 0 (Egr2 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 169238-82-8 (Neurogenic differentiation factor 1)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism
MH  - Brain/abnormalities/cytology/*metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - CCAAT-Enhancer-Binding Protein-alpha/genetics/metabolism
MH  - CCAAT-Enhancer-Binding Protein-beta/genetics/metabolism
MH  - CCAAT-Enhancer-Binding Proteins/genetics/*metabolism
MH  - Cell Differentiation/genetics
MH  - Cells, Cultured
MH  - Dendrites/metabolism/pathology
MH  - Early Growth Response Protein 1/genetics/metabolism
MH  - Early Growth Response Protein 2/genetics/metabolism
MH  - Gene Expression Regulation, Developmental/genetics
MH  - Genes, Immediate-Early/*genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - NIH 3T3 Cells
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Neurons/cytology/*metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins c-fos/genetics/metabolism
MH  - Receptor, trkB/genetics/*metabolism
MH  - Serum Response Element/genetics
MH  - Transcriptional Activation/genetics
PMC - PMC1796876
EDAT- 2007/01/27 09:00
MHDA- 2008/12/17 09:00
PMCR- 2007/01/25
CRDT- 2007/01/27 09:00
PHST- 2006/10/07 00:00 [received]
PHST- 2007/01/25 00:00 [accepted]
PHST- 2007/01/27 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2007/01/27 09:00 [entrez]
PHST- 2007/01/25 00:00 [pmc-release]
AID - 1749-8104-2-4 [pii]
AID - 10.1186/1749-8104-2-4 [doi]
PST - epublish
SO  - Neural Dev. 2007 Jan 25;2:4. doi: 10.1186/1749-8104-2-4.