@article {126, title = {REST Regulates Non-Cell-Autonomous Neuronal Differentiation and Maturation of Neural Progenitor Cells via Secretogranin II.}, journal = {J Neurosci}, volume = {35}, year = {2015}, month = {2015 Nov 4}, pages = {14872-84}, abstract = {

UNLABELLED: RE-1 silencing transcription factor (REST), a master negative regulator of neuronal differentiation, controls neurogenesis by preventing the differentiation of neural stem cells. Here we focused on the role of REST in the early steps of differentiation and maturation of adult hippocampal progenitors (AHPs). REST knockdown promoted differentiation and affected the maturation of rat AHPs. Surprisingly, REST knockdown cells enhanced the differentiation of neighboring wild-type AHPs, suggesting that REST may play a non-cell-autonomous role. Gene expression analysis identified Secretogranin II (Scg2) as the major secreted REST target responsible for the non-cell-autonomous phenotype. Loss-of-function of Scg2 inhibited differentiation in vitro, and exogenous SCG2 partially rescued this phenotype. Knockdown of REST in neural progenitors in mice led to precocious maturation into neurons at the expense of mushroom spines in vivo. In summary, we found that, in addition to its cell-autonomous function, REST regulates differentiation and maturation of AHPs non-cell-autonomously via SCG2.

SIGNIFICANCE STATEMENT: Our results reveal that REST regulates differentiation and maturation of neural progenitor cells in vitro by orchestrating both cell-intrinsic and non-cell-autonomous factors and that Scg2 is a major secretory target of REST with a differentiation-enhancing activity in a paracrine manner. In vivo, REST depletion causes accelerated differentiation of newborn neurons at the expense of spine defects, suggesting a potential role for REST in the timing of the maturation of granule neurons.

}, keywords = {Animals, Cell Differentiation, Cells, Cultured, Female, Hippocampus, Mice, Mice, Inbred C57BL, Neural Stem Cells, Neurogenesis, Neurons, Rats, Wistar, Repressor Proteins, Secretogranin II}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.4286-14.2015}, author = {Kim, Hyung Joon and Denli, Ahmet M and Wright, Rebecca and Baul, Tithi D and Clemenson, Gregory D and Morcos, Ari S and Zhao, Chunmei and Schafer, Simon T and Gage, Fred H and Kagalwala, Mohamedi N} } @article {183, title = {Selection of distinct populations of dentate granule cells in response to inputs as a mechanism for pattern separation in mice.}, journal = {Elife}, volume = {2}, year = {2013}, month = {2013}, pages = {e00312}, abstract = {

The hippocampus is critical for episodic memory and computational studies have predicted specific functions for each hippocampal subregion. Particularly, the dentate gyrus (DG) is hypothesized to perform pattern separation by forming distinct representations of similar inputs. How pattern separation is achieved by the DG remains largely unclear. By examining neuronal activities at a population level, we revealed that, unlike CA1 neuron populations, dentate granule cell (DGC) ensembles activated by learning were not preferentially reactivated by memory recall. Moreover, when mice encountered an environment to which they had not been previously exposed, a novel DGC population-rather than the previously activated DGC ensembles that responded to past events-was selected to represent the new environmental inputs. This selection of a novel responsive DGC population could be triggered by small changes in environmental inputs. Therefore, selecting distinct DGC populations to represent similar but not identical inputs is a mechanism for pattern separation. DOI:http://dx.doi.org/10.7554/eLife.00312.001.

}, keywords = {Animals, Behavior, Animal, Brain Mapping, CA1 Region, Hippocampal, Conditioning (Psychology), Cues, Dentate Gyrus, Environment, Fear, Gene Expression Regulation, Genes, Reporter, Memory, Memory, Episodic, Mental Recall, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Neural Pathways, Neurons, Pattern Recognition, Physiological, Time Factors}, issn = {2050-084X}, doi = {10.7554/eLife.00312}, author = {Deng, Wei and Mayford, Mark and Gage, Fred H} }