Regulation of neural progenitor cell development in the nervous system

Abstract

The mammalian telencephalon, which comprises the cerebral cortex, olfactory bulb, hippocampus, basal ganglia, and amygdala, is the most complex and intricate region of the CNS. It is the seat of all higher brain functions including the storage and retrieval of memories, the integration and processing of sensory and motor information, and the regulation of emotion and drive states. In higher mammals such as humans, the telencephalon also governs our creative impulses, ability to make rational decisions, and plan for the future. Despite its massive complexity, exciting work from a number of groups has begun to unravel the developmental mechanisms for the generation of the diverse neural cell types that form the circuitry of the mature telencephalon. Here, we review our current understanding of four aspects of neural development. We first begin by providing a general overview of the broad developmental mechanisms underlying the generation of neuronal and glial cell diversity in the telencephalon during embryonic development. We then focus on development of the cerebral cortex, the most complex and evolved region of the brain. We review the current state of understanding of progenitor cell diversity within the cortical ventricular zone and then describe how lateral signaling via the Notch‐Delta pathway generates specific aspects of neural cell diversity in cortical progenitor pools. Finally, we review the signaling mechanisms required for development, and response to injury, of a specialized group of cortical stem cells, the radial glia, which act both as precursors and as migratory scaffolds for newly generated neurons.

Neuronal stem cells in the central nervous system and in human diseases

“…As a conservative neuronal developmental signaling pathway, Notch plays a critical role in neural stem cell maintenance (Corbin et al, 2008). With the theory that tumors originate from stem cells, the Notch signaling pathway has been recently studied in the aspect of its relevance in glioma formation.…”

Endothelial cells promote neural stem cell proliferation and differentiation associated with VEGF activated Notch and Pten signaling

“…Notch signaling is thought to maintain ''stemness'' and to prevent exit from the cell cycle and maturation (Basak and Taylor, 2009). However, its role in adult neurogenesis remains unclear, primarily because Notch plays so many other roles in maturation, neuroplasticity, and survival (Carlson and Conboy, 2007;Corbin et al, 2008 (Backman et al, 2001;Kwon et al, 2001;Groszer et al, 2001). Conditional knockout of Pten in neural stem cells revealed that Pten is indispensable for proper control of neural stem cell proliferation and self-renewal in the developing brain (Groszer et al, 2001).…”

Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun

“…The Notch signalling pathway controls neural differentiation and is known to maintain NSC character and to inhibit neurogenesis. The Notch-Hes pathway is necessary for self-renewing cell division and thus, maintenance of the neural precursor population [10][11][12][13] . However, the significance of the regulation of c-Jun, Notch and other substrates by SCF(Fbw7) during neurogenesis has remained unclear to date.…”