title: Distinct and overlapping gene regulatory networks in BMP- and HDAC-controlled cell fate determination in the embryonic forebrain.
abstract: BACKGROUND
  Both bone morphogenetic proteins (BMPs) and histone deacetylases (HDACs) have previously been established to play a role in the development of the three major cell types of the central nervous system: neurons, astrocytes, and oligodendrocytes. We have previously established a connection between these two protein families, showing that HDACs suppress BMP-promoted astrogliogenesis in the embryonic striatum. Since HDACs act in the nucleus to effect changes in transcription, an unbiased analysis of their transcriptional targets could shed light on their downstream effects on BMP-signaling.
  
  
  RESULTS
  Using neurospheres from the embryonic striatum as an in vitro system to analyze this phenomenon, we have performed microarray expression profiling on BMP2- and TSA-treated cultures, followed by validation of the findings with quantitative RT-PCR and protein analysis. In BMP-treated cultures we first observed an upregulation of genes involved in cell-cell communication and developmental processes such as members of BMP and canonical Wnt signaling pathways. In contrast, in TSA-treated cultures we first observed an upregulation of genes involved in chromatin modification and transcription. Interestingly, we could not record direct changes in the protein levels of canonical members of BMP2 signaling, but we did observe an upregulation of both the transcription factor STAT3 and its active isoform phospho-STAT3 at the protein level.
  
  
  CONCLUSIONS
  STAT3 and SMAD1/5/8 interact synergistically to promote astrogliogenesis, and thus we show for the first time that HDACs act to suppress BMP-promoted astrogliogenesis by suppression of the crucial partner STAT3.
authors: Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, 69120 Heidelberg, Germany. Kerry.Tucker@urz.uni-heidelberg.de
authors: Catharina
authors: C
authors: Scholl
authors: Kathrin
authors: K
authors: Weiβmüller
authors: Pavlo
authors: P
authors: Holenya
authors: Maya
authors: M
authors: Shaked-Rabi
authors: Kerry L
authors: KL
authors: Tucker
authors: Stefan
authors: S
authors: Wölfl
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D016548:Prosencephalon / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D051902:Smad5 Protein / Q000235:genetics / Q000378:metabolism; D051904:Smad8 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D050796:STAT3 Transcription Factor; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051902:Smad5 Protein; D051904:Smad8 Protein; C012589:trichostatin A; D006655:Histone Deacetylases