Gliogenesis

Gliogenesis is the generation of non-neuronal glia populations derived from multipotent neural stem cells.Gliogenesis results in the formation of non-neuronal glia populations derived from multipotent neural stem cells. In this capacity, glial cells provide multiple functions to both the central nervous system (CNS) and the peripheral nervous system (PNS). Subsequent differentiation of glial cell populations results in function-specialized glial lineages. Glial cell-derived astrocytes are specialized lineages responsible for modulating the chemical environment by altering ion gradients and neurotransmitter transduction. Similarly derived, oligodendrocytes produce myelin, which insulates axons to facilitate electric signal transduction. Finally, microglial cells are derived from glial precursors and carry out macrophage-like properties to remove cellular and foreign debris within the central nervous system ref. Functions of glial-derived cell lineages are reviewed by Baumann and Hauw. Gliogenesis itself, and differentiation of glial-derived lineages are activated upon stimulation of specific signaling cascades. Similarly, inhibition of these pathways is controlled by distinct signaling cascades that control proliferation and differentiation. Thus, elaborate intracellular-mechanisms based on environmental signals are present to regulate the formation of these cells. As regulation is much more known in the CNS, its mechanisms and components will be focused on here. Understanding the mechanisms in which gliogenesis is regulated provides the potential to harness the ability to control the fate of glial cells and, consequently, the ability to reverse neurodegenerative diseases.Following the generation of neural stem cells, an option is presented to proceed to enter neurogenesis and form new neurons within the CNS, shift into gliogenesis, or remain in a pluripotent cell state. The mechanisms determining the ultimate fate of neural stem cells are conserved among both invertebrate and vertebrate species and are determined from extracellular cues generated from neighboring cells. Most work to derive such mechanisms, however, began with invertebrate models. Conclusions reached from these studies have directed attention to specific signaling molecules and effector pathways that are responsible for mediating the cellular events required for maintaining or changing the neural stem cell fate.To ensure proper temporal differentiation as well as correct quantities of glial cell formation, gliogenesis is subjected to stringent regulatory mechanisms. Proneural factors are expressed in high concentrations during times in which glial cells are not to form or neuron development is needed. These protein signals function to inhibit many of the signals utilized during the induction of gliogenesis. Additionally, the properties and abundance of receptor molecules that mediate gliogenesis are altered, consequently disrupting propagation of induction signals.Recent work has demonstrated abnormalities in the signaling pathways responsible for gliogenesis and neurogenesis could contribute to the pathogenesis of neurodegenerative diseases and tumor development within the nervous system. Recognizing the distinct pathways controlling neural stem fate, as discussed above, provides one the opportunity to intervene in the pathogenesis of these diseases.Understanding the pathology of these neurodegenerative diseases and establishment of therapeutic interventions require recognition of the processes of induction and inhibition of gliogenesis and the regulating mechanisms coordinating the intricate system established from both actions. Cell replacement strategies are now intensely studied as a possible therapeutic intervention of glial associated neurodegenerative disorders and glial tumors. Similar to any novel strategy, however, set-backs and liabilities accompany the promises this technique withholds. For cell replacement to function efficiently and demonstrate robust results, introduced cells must be 1) generated in sufficient yield and 2) immunocompatible with the host and 3) able to sustain self-growth. New perspectives within stem cell biology and gliogenesis regulation have provided new insights within the past decade to begin addressing these challenges. Reprogramming terminally differentiated neural lineages back to neural stem cells permits regeneration of a multipotent self-lineage that can be redirected to cellular-fates affected during neurogenerative diseases, oligodendrocytes with MS patients or astrocytes in those affected with Alzheimer's, in the presence of proper environmental signals.