Gliogenesis
Glial cell-derived astrocytes are specialized lineages responsible for modulating the chemical environment by altering ion gradients and neurotransmitter 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.
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.
In the presence of ligand effectors, the intracellular domain of the receptor is cleaved and sequestered to the nucleus where it acts to influence expression of transcription factors required for gliogenesis.
Transcription factors synthesized as a result of the Notch signaling cascade bind to promoters of genes responsible for glial determination.
[7] As noted for receptor-proteins, in vivo interactions among different growth factor responsible for gliogenesis and other cell fates produce very different roles than when isolated.
To ensure proper temporal differentiation as well as correct quantities of glial cell formation, gliogenesis is subjected to stringent regulatory mechanisms.
[11] It has been shown Notch receptors require 50-fold higher concentrations of ligand effectors to initiate differentiation responses similar to that of developmentally earlier neural stem cells.
Consequently, neural stem cells have developed a general mechanism limiting further differentiation after intense specialization during the early developmental periods.
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.
[17][18] Recognizing the distinct pathways controlling neural stem fate, as discussed above, provides one the opportunity to intervene in the pathogenesis of these diseases.
[19] The subventricular zone (SVZ) of the forebrain is of special interest when evaluating errant gliogenic pathways as it is the largest store of neural stem cells in the brain.
[23] Consequently, a reduction of glial-derived oligodendrocytes, among others, compromise maintenance of myelin production for axon insulation, a hallmark phenotype among MS patients.
Linskey reviews both the genetic contributions and phenotypic observations of glioma [27] In non-carcinogenic neural stem cells, key regulatory mechanisms prevent uncontrolled gliogenic proliferation.
[30] New perspectives within stem cell biology and gliogenesis regulation have provided new insights within the past decade to begin addressing these challenges.
