The downregulation of oligoden drocyte specific genes in our experiments is in accord ance with a reduction of oligodendrocytes that was observed by ourselves and others. Many of these oligodendrocyte specific genes were not only sig nificantly down regulated upon TSA treatment but also after BMP2 treatment, especially after 24 h. This also corresponds with together previous reports showing that BMPs promote the production of astroglia while inhibiting oligodendrocyte differentiation. The fact that treat ment with BMP2 and TSA downregulates oligodendro cyte specific genes seems to be a common feature of both compounds, but it still needs to be clarified if the demonstrated effect is due to the same regulatory mech anism.

Upregulation of Wnt5a, Wisp1, and other genes from Wnt signaling in our experiments could give a cer tain indication that the regulatory mechanism could be related in both cases. Wnt signaling leads to the sup pression of oligodendrocyte differentiation and promotes neuronal and astroglial differentiation. The connec tion between BMP and Wnt signaling as well as be tween HDACs and Wnt signaling had been shown to be important for astroglial and oligodendroglial line age commitment, and it will be of great interest to examine whether HDACs and BMPs share a common pathway in the regulation of oligodendrocyte differenti ation, as we have shown for astrocyte differentiation in this work. Conclusions In this study we have delineated at the genomic tran scriptome level the responses to two different com pounds that we and others have shown to lead to similar biological outcomes in the differentiation of neural pro genitor cells to neurons, astrocytes and oligodendrocytes in the embryonic forebrain.

Interestingly, the range of responses to BMP2 and to the global HDAC inhibitor TSA were dramatically different, with BMP leading to an upregulation of genes involved in cell cell communica tion and developmental processes while TSA resulted in an upregulation of genes involved in chromatin modifi cation and transcription. Surprisingly, the biological con vergence of the genomic responses could not be reduced to canonical BMP signaling through Smad1/5/8 activa tion, rather HDAC inhibition and BMP2 signaling converge through Stat3 and Smad1/5/8 mediated signal ing and Id1 activation which increases astrogliogenesis from neural stem cells.

This result explains the similar outcomes of HDAC inhibition and BMP with respect to astrogliogenesis, and the microarray profiling also sug gests new pathways, for example Wnt signaling, which may be Anacetrapib of further relevance for the interaction between these two developmentally crucial protein families. Methods Mouse lines All animal experiments were conducted in compliance with the regulations of the state of Baden W��rttemberg, Germany. We employed C57BL/6 J mice.