Neurogenesis, or the process by which neural stem cells (NSCs) give rise to the neurons of the central nervous system (CNS), initially occurs during embryonic development, termed development or prenatal neurogenesis, and continues throughout adulthood, termed postnatal and adult neurogenesis, with marked differences. During developmental neurogenesis, ectoderm-derived neuroepithelial cells of the ventricular zone (VZ) elongate and generate the primary NSCs of the mammalian CNS, known as radial glial cells (RGCs). In addition to amplifying through self-renewal, RGCs directly and indirectly generate neurons through asymmetrical division resulting in one self-renewing daughter cell alongside either a post-mitotic neuron or an intermediate progenitor cell (IPC), respectively.
While IPCs retain the capacity to self-amplify through symmetrical division, allowing for expansion of cortical size, they primarily differentiate symmetrically into neurons, oligodendrocyte progenitors or astrocyte progenitors. New neurons move to their ﬁnal destinations through a process known as radial migration, whereupon they mature fully and develop the deﬁning, information-transmitting axons and dendrites. Unlike developmental neurogenesis, adult neurogenesis is restricted to the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the striatum, where new neurons are integrated into existing cortical framework.
The ability of NSCs to generate the neurons and glia that constitute the CNS places them at the forefront of neuro-developmental research, neuro-disease modeling and regenerative medicine; underscoring the need for developing efﬁcient methods for obtaining NSCs.The ability of NSCs to generate the neurons and glia that constitute the CNS places them at the forefront of neuro-developmental research, neuro-disease modeling and regenerative medicine; underscoring the need for developing efﬁcient methods for obtaining NSCs.
Currently, three major sources for NSCs have been identified:
1. Isolation from primary neural tissues followed by exposure to FGF-basic and EGF to induce proliferation, self-renewal, and expansion.
2. Differentiation from pluripotent stem cells, either by embryoid body formation or monolayer culture.
3. Direct transdifferentiation from somatic cells through induction by:
- Expression of speciﬁc transcription factors, usually in combination with small molecules.
- Chemical transdifferentiation using a cocktail of only small molecules.
- Growth factors in combination with a three-dimensional culture system.