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Neural Stem Cells



Rejuvenation of Regeneration in the Aging Central Nervous System

From Cell Stem Cell
By Stuart P. Atkinson

Oligodendrocytes precursor cells (OPCs) differentiate into oligodendrocytes with remyelination capabilities which, in the adult central nervous system (CNS), restores conduction, prevents axonal degradation and promotes functional recovery. Reduction in this capacity in aging (Sim et al) leads to demyelinated neurons and axonal degeneration, which is understood to be mediated in part by environmental signals (Hinks and Franklin). This suggests that exogenous factors may be able to reverse this age-associated decline in function, which has now been addressed in an article (Ruckh and Zhao et al) in Cell Stem Cell by researchers in the laboratory of Amy J. Wagers (Howard Hughes Medical Institute) and Robin J.M. Franklin (MRC Centre for Stem Cell Biology and Regenerative Medicine).

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

Article Focus for this Month’s Edition of Stem Cells

Paper commentary by Carla B. Mellough

The subventricular zone (SVZ) is a multicellular structure that lines the lateral walls of the lateral ventricles of the brain. SVZ ependymal cells face the ventricular lumen and are involved in the production and circulation of cerebrospinal fluid. Further, the SVZ is an established site of adult neurogenesis, boasting the largest population of proliferative cells in the brain of mature rodents, monkeys and humans. The neural precursor cells (NPCs) of the SVZ produce neuroblasts which migrate to the olfactory bulb via the rostral migratory stream (RMS). These ordinarily act to replenish olfactory neurons, however following central nervous system (CNS) damage they become capable of migrating towards ectopic sites of injury. The mobilisation and guidance of NPCs towards a distinct neural destination involves numerous external signals which must be integrated and translated by neuroblasts to produce an appropriate response, allowing specific and directed migration. The Rho-GTPase family of molecules and their related regulatory members such as the Rac and PIk3 proteins have previously been demonstrated to influence cell migration by regulating the translation of external signals into cytoskeletal reorganisation, yet their role in the migration of neuroblasts through the adult RMS had not yet been established. In the February edition of Stem Cells, new results by Leong et al. from Ann Turnley’s laboratory at the Centre for Neuroscience at The University of Melbourne, begin to reveal the role of the Rho-GTPase pathway in the migration of adult mouse SVZ NPCs.

Nutritional Signals Regulate Stem Cell Quiescence and Proliferation

It has been over ten years since the physiological link between nutritional input and growth and development in Drosophila was established, yet the mechanisms downstream of nutritional stimuli that act to regulate the growth of the organism were unknown. Results published recently in Cell from Chell and Brand at the Gurdon Institute and Department of Physiology, Development and Neuroscience at the University of Cambridge now shed light on the identity and action of these nutrition-dependent signals. Their research reveals that following nutritional stimulus neural stem cells (or neuroblasts) exit quiescence in response to the release of insulin/insulin-like growth factor (IGF)-like peptides (ILP2 and ILP6) from adjacent glial cells. The authors demonstrate that these peptides elicit their effect by means of the insulin-like receptor on glial cells and that this activates the phosphoinositide 3-kinase (PI3K)-Akt pathway. Whilst the authors noted elevated PI3K activation as neuroblasts were entering the proliferation stage, absence of the PI3K catalytic subunit maintained neuroblasts in the quiescent state. Their results provide insight into systemic control of neuroblasts by nutrition, and highlights glia as a key regulator of the stem cell niche.


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