Development

A Positive Conversion

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Science  25 Jan 2013:
Vol. 339, Issue 6118, pp. 374
DOI: 10.1126/science.339.6118.374-b
CREDIT: Y. XUE ET AL., CELL 152 (17 JANUARY 2013) © 2013 ELSEVIER INC.

Tracing the pathways that lead to neuronal differentiation is important both for understanding neurodevelopment and because of the implications for developing therapeutics for degenerative diseases such as Parkinson's and Alzheimer's disease. Recent experiments have demonstrated that a group of transcription factors are capable of converting fibroblasts into neuronal cells in vitro and that the process involves microRNAs. To better understand the process, Xue et al. studied the role of a particular polypyrimidine-tract–binding protein (PTB) that is repressed during normal brain development by a microRNA, miR-124, and is known to be involved in the regulation of splicing of mRNA. Knockdown of PTB expression in HeLa cells, human embryonic carcinoma stem cells, mouse neural progenitor cells, and primary mouse embryonic fibroblasts induced a neuronal morphology and, for two of the cell types, expression of neuronal markers as well as synaptic activity. PTB not only acts as a target of miR-124, but also serves as a negative regulator of miRNA-124 and other microRNAS. An important consequence of PTB inhibition is the disassembly of the REST complex, which normally acts to silence neuronal genes in nonneuronal cells. Thus, the net result is to change a negative regulatory loop into a positive one and induce neuronal differentiation.

Cell 10.1016/j.cell.2012.11.045 (2013).

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