Neurogenesis in the Central Nervous System: Cell Cycle Progression/Exit and Differentiation of Neuronal Progenitors

Abstract

This chapter focuses on recent developments shedding light on the basic mechanisms occurring during the early stages of embryonic central nervous system (CNS) development leading to neuroepithelial cell proliferation and subsequent differentiation, as well as on the molecular determinants and signaling pathways regulating cell cycle progression/exit and cell fate determination. The morphogeneses of the embryonic spinal cord and cerebral cortex, which are two of the best characterized systems of CNS development, are used as complementary paradigms to describe the regulation of cell cycle progression/exit and differentiation, the types of cells participating in these mechanisms, as well as their divisional mode and differentiation potential. Particular emphasis is also given in describing the role and neurogenic potential of a revisited precursor cell type, namely the radial glia, as well as the contribution of neural stem cells (NCS) in adult neurogenesis. These two novel aspects of neurogenesis have been characterized during the last decade and have revolutionized the scenario concerning the timing of neuronal production in mammals and the cell types participating in this process. Most important, through progress in these fields it has been discovered that precursor cells residing in discrete regions of the adult brain are able to generate specific sub-classes of neurons throughout life under physiological conditions, but have also the initial intrinsic potential to contribute to neuronal regeneration under pathological conditions if appropriately stimulated. The intimate link between cell cycle control and neurogenesis during CNS development and the characterization of dual function molecules both instructing cell cycle exit and differentiation towards the neuronal lineage will be also discussed. The above link has received increasing scientific attention lately, as it is a key mechanism regulating the spatiotemporal networks that coordinate the size of different CNS regions. Finally, the developmental cell death is also discussed as an alternative cell number control mechanism also contributing to the right number of differentiated neuronal and glial cells at the correct CNS areas.