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Published online: 23 April 2008 | doi:10.1038/nchina.2008.92

Neural differentiation: Nogo might mean yes

Wei Zeng

Introduction

© (2008) Wang et al.

In neural stem-cell therapy, injured neurons are replaced by stem cells that will differentiate into neurons after transplantation. With the current technology, however, only a small portion of transplanted stem cells differentiate into neurons as the central nervous system recovers. Most stem cells differentiate into glial cells. Jianwu Dai at the Chinese Academy of Sciences in Beijing and co-workers¹ have found the protein Nogo-66 to be responsible for promoting stem cells to become glial cells instead of neurons.

The growth inhibitory factor Nogo-A, secreted by glial cells, has been known to stop axons in injured neurons from regenerating through its Nogo-66 domain. The researchers found that applying Nogo-66 in vitro would promote cultured stem cells to differentiate into glial cells. Blocking NgR — the Nogo-66 receptor in the cell membrane (see image, coloured in green) — would stop cultured stem cells from differentiating into glial cells.

Through further experiments, the researchers showed that Nogo-66 proteins bound to NgRs, thus recruiting binding between the enzyme mTOR, and the transcriptional factor STAT3 in the cytoplasm to form a complex; mTOR helped STAT3 undergo phosphorylation. The phosphorylated STAT3 would then enter the nucleus and trigger glial differentiation.

The findings show that endogenous glial cells influence stem cells to become glial cells through the secretion of Nogo-66, which might be a potential target for increasing neural differentiation.

The authors of this work are from:
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.

Reference

1. Wang, B. et al. Nogo-66 promotes the differentiation of neural progenitors into astroglial lineage cells through mTOR–STAT3 pathway. PLoS ONE 3, e1856 (2008). | Article | PubMed | ChemPort |