BMP2-mediated alteration in the developmental pathway of fetal mouse braincells from neurogenesis to astrocytogenesis

We show that when telencephalic: neural progenitors are briefly exposed to bone morphogenetic protein 2 (BMP2) in culture, their developmental fate is changed from neuronal cells to astrocytic cells. BMP2 significantly reduce d the number of cells expressing microtubule-associated protein 2, a neuron al marker, and cells expressing nestin, a marker for undifferentiated neura l precursors, but BMP2 increased the number of cells expressing S100-beta, an astrocytic marker. In telencephalic neuroepithelial cells, BMP2 up-regul ated the expression of negative helix-loop-helix (HLH) factors Id1, Id3, an d Hes-5 (where Hes is homologue of hairy and Enhancer of Split) that inhibi ted the transcriptional activity of neurogenic HLH transcription factors Ma sh1 and neurogenin. Ectopic expression of either Id1 or Id3 (where Id is in hibitor of differentiation) inhibited neurogenesis of neuroepithelial cells , suggesting an important role for these HLH proteins in the BMP2-mediated changes in the neurogenic fate of these cells. Because gliogenesis in the b rain and spinal cord, derived from implanted neural stem cells or induced b y injury, is responsible for much of the failure of neuronal regeneration, this work may lead to a therapeutic strategy to minimize this problem.