Author:
Nakashima Kinichi,Takizawa Takumi,Ochiai Wataru,Yanagisawa Makoto,Hisatsune Tatsuhiro,Nakafuku Masato,Miyazono Kohei,Kishimoto Tadamitsu,Kageyama Ryoichiro,Taga Tetsuya
Abstract
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 reduced the number of cells expressing
microtubule-associated protein 2, a neuronal marker, and cells
expressing nestin, a marker for undifferentiated neural precursors, but
BMP2 increased the number of cells expressing S100-β, an astrocytic
marker. In telencephalic neuroepithelial cells, BMP2 up-regulated the
expression of negative helix–loop–helix (HLH) factors Id1, Id3, and
Hes-5 (where Hes is homologue of hairy and Enhancer of Split) that
inhibited the transcriptional activity of neurogenic HLH transcription
factors Mash1 and neurogenin. Ectopic expression of either Id1 or Id3
(where Id is inhibitor 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 brain and spinal cord, derived from
implanted neural stem cells or induced by injury, is responsible for
much of the failure of neuronal regeneration, this work may lead to a
therapeutic strategy to minimize this problem.
Publisher
Proceedings of the National Academy of Sciences
Cited by
314 articles.
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