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

Kinichi Nakashima, Takumi Takizawa, Wataru Ochiai, Makoto Yanagisawa, Tatsuhiro Hisatsune, Masato Nakafuku, Kohei Miyazono, Tadamitsu Kishimoto, Ryoichiro Kageyama, Tetsuya Taga

Research output: Contribution to journalArticlepeer-review

297 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5868-5873
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number10
DOIs
Publication statusPublished - May 8 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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