An oblique view on the role of spindle orientation in vertebrate neurogenesis

Neurogenesis is a dynamic process that produces a diverse number of glial and neural cell types from a limited number of neural stem cells throughout development and into adulthood. After an initial period of amplification through symmetric division, neural stem cells rely on asymmetric modes of division to self-renew while producing more committed progeny. Understanding the molecular mechanisms regulating the choice between symmetric and asymmetric modes of division is essential to understand human brain development and pathologies, and to explain the increasing cortical complexity observed in evolution. A popular model states the existence of a causal relationship between the orientation of the axis of division of stem cells and the fate of their progeny in many different tissues, but the validity of the model in neural stem cells is not clear. In this review, we briefly present the diversity of neural stem cells and intermediate progenitors in the developing central nervous system. We then draw a historic overview of the assumed causal relationship between spindle orientation and fate determination. We show how this prompted a search for regulators of spindle orientation, and present the current state of knowledge on the mechanism. Finally, we review data on the effect of defective spindle orientation and try to integrate conflicting observations by presenting alternative mechanisms that may regulate the choice between symmetric and asymmetric outcomes