REST regulation of neural development: From outside-in?

The RE1 Silencing Transcription Factor (REST) is a master regulator of neuronal and glial fate specification that acts at multiple levels of stem cell differentiation, through the engagements of a plethora of cofactors and histone modifying proteins. Buckley and colleagues now show that low levels of REST are required even after the transition from embryonic stem cells to more committed neural progenitors, as well as neurogenesis. Generations of nestin-positive, followed by III-tubulin-positive as well as MAP2-positive phenotype are impeded by REST ablation, and REST-depleted neural stem cells are defective in adherence, migration and survival. These defects can be rescued by exogenous laminin. The findings shed new light on a previously underemphasized aspect of REST function, namely extracellular matrix regulation during neural differentiation.